Welcome from the President
On behalf of our Executive Board, Advisory Board, Committee Chairs, and all of our leaders past and present, it is a great
pleasure to welcome you to the 17th Annual Meeting of the International Society for Cellular Therapy at the De Doelen
Congress Centre in Rotterdam. We are delighted to be in this magnificent port city of Rotterdam in the spring time and
anticipate an extraordinary scientific experience over the coming days.
Cell therapy continues to grow at rapid pace and ISCT continues to be the premier global society promoting the principles
and practice of all areas within the vast arena of cell therapy. Every year, we gather at a wonderful destination around
the world to talk about our work, rekindle old friendships, and make new ones. These yearly events are the forum for us
to learn about new breakthroughs, and exchange our thoughts and ideas. This year Ineke, Massimo and Fred have done
an outstanding job in producing what promises to be the best meeting ever! We truly have something for everyone! The
plenary sessions will present the most outstanding science in cell therapy covering a wide array of topics from stem cells to
immunotherapy. You will hear about everything from the basic research in cell therapy to the translation this knowledge
into the clinics and, most importantly, how cell therapy is impacting the practice of medicine. The oral abstract sessions
highlight the very best “cutting-edge” science at the meeting and the poster sessions generate the informal exchanges
that stimulate the ideas which ultimately move the field forward. Our workshops provide the opportunity to discuss and
debate the controversies in the field leaving all participants with a broader view than when they arrived. We continue to
have a special track at the meeting focused on the cell processing technologists, the unsung heroes of cell therapy. We
pay special attention to the legal and regulatory issues that are required to move cell therapy into the clinics…after all,
we are the translational cell therapy society!
Always remember that we, the society members, are ISCT. Indeed, I believe the splendor of ISCT is our members from
around the world…Europe, our hosts this years, Asia, Australia, New Zealand, North and South America… and all walks
of cell therapy…academia and industry. There is no limit to what we can accomplish once the professional lines are
erased and the geographical barriers eliminated. We are delighted to have everyone here in Rotterdam, but if you’re not a
member of ISCT, I encourage you to join us so you too can enjoy the many benefits of membership. You will not regret it!
Finally, I would like to thank my good friends, Ineke, Massimo, Fred, and the entire Organizing Committee for their
extraordinary effort leading this Rotterdam meeting. I offer a most special “thank you” to all of our industry partners
on the Commercialization Committee and our wonderful corporate sponsors of our Annual Meeting. Without your
unwavering support, we could not do our job promoting cell therapy to the world.
So go! Enjoy! Rotterdam awaits!!
Edwin Horwitz
ISCT President
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May 18 – 21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
www.celltherapy2011.com
Table of Contents
General Conference Information................................................................................ 2
Continuing Education Information............................................................................. 3
Organizing Committee............................................................................................... 6
Invited Speakers and Chairs........................................................................................ 7
Oral Presenters........................................................................................................... 8
Program..................................................................................................................... 9
Plenary Session Synopses......................................................................................... 16
Technical Session Synopses...................................................................................... 22
Workshop Session Synopses..................................................................................... 24
Technical Applications Track Synopses...................................................................... 26
Strategies for Commercialization Track Synopses...................................................... 29
Meeting Room Directory.......................................................................................... 32
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General Conference
Information
The conference registration desk is located in the Willem
Burger Hall. Registration hours are as follows:
4:00pm – 7:00pm
7:00am – 7:00pm
7:00am – 4:00pm
7:00am – 4:00pm
7:00am – 3:00pm
general conference information
Included in your Annual Meeting
registration fee:
2
•
•
•
Access to the Welcome Reception
Access to all Technical Breakfasts, Technical
Applications Track Sessions, Strategies for
Commercialization Track Sessions, Workshops,
Plenary Sessions, Poster Sessions, Oral Abstract
Sessions, Exhibit Hall, Corporate Symposia and
Corporate Tutorials
Lunch (May 19-21) and all coffee breaks and
refreshments served in the Exhibit Hall
(Please note that breakfast is not served at the De Doelen. Breakfast is
included with your stay at The Manhattan Hotel Rotterdam or the
Hilton Rotterdam Hotel)
•
•
•
•
•
Academic Program
Corporate Conference guide
2011 Annual Meeting Abstract issue of
Cytotherapy, the official journal of ISCT
Delegate List (for download online)
Delegate Bag
Exhibit-only attendees receive:
•
•
•
Access to the Exhibit Hall including the Welcome
Reception on Wednesday May 18th
Conference meals and refreshments served in the
exhibit hall
Corporate Conference Guide
Additional registration fees required for:
Please visit the registration desk to purchase registrations or tickets
•
•
Wednesday May 18th – Welcome Address
and Reception
Admission:
Registration
Tuesday May 17 Wednesday May 18
Thursday May 19
Friday May 20
Saturday May 21
Social Events
Pre-Conference Events on Wednesday May 18th:
FACT/JACIE Cellular Therapy Workshop and the
Global Regulatory Perspectives Workshop
Gala Event on Friday May 20th
Free for all conference delegates
Where & When:
7:00pm – 7:30pm: Welcome Address in the Jurriaanse Zaal
7:30pm – 9:30pm: Welcome Reception in the Exhibit Hall
Cocktails and hors d’oeuvres will be served
Friday May 20th – Gala Event
Admission:
$100 USD (€ 72) for conference delegates
$125 USD (€ 90) for non-conference delegates
Where & When:
6:00pm – 7:30pm: Cocktail reception at Rotterdam City Hall
Bus transportation from City Hall to SS Rotterdam included
7:30pm – 11:00pm: Dinner and live music at the SS Rotterdam
Bus transporation back to the Hilton Rotterdam Hotel and Manhattan Hotel
Rotterdam included
Networking Session for
Operations Specialists
Saturday May 21st
ADMISSION:
All delegates welcome to attend
WHERE & WHEN:
11:45am – 1:15pm: Fortis Bank Zaal
Target: Those who work in processing and collection facilities,
quality assurance, regulatory compliance, etc. to bring cellular
therapy products to patients, ranging from those working ‘in
the hood’ to the Directors who oversee their work.
Goal: To learn more about what the needs are of this critical
segment of the ISCT membership, and figure out how ISCT
can help meet those needs.
Social Media
ISCT is pleased to offer conference delegates up-to-date
news feeds via Twitter and our blog. Follow us on twitter or
visit our blog for program updates, conference news, and to
provide feedback on the program!
Twitter: @ISCT2011 Hashtag: #ISCT2011
Blog: http://celltherapy2011.weebly.com/
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Continuing Medical Education
CME
Target Audience
This activity has been designed to meet the educational needs of clinicians, scientists, researchers, technologists, regulatory
professionals and industry experts working in the cell therapy field.
Statement of Need/Program Overview
Because of its focus on emerging cell therapies, ISCT’s Annual Meeting will provide the most current information regarding
a wide range of therapies – from tissue engineering to immunotherapy to cancer stem cells - to researchers and clinicians
alike. Sessions will focus on efficacy of current therapies, challenges and successes in clinical trials and insights into practical
roadblocks to large scale product development.
Educational Objectives
After completing this activity, the participant should be better able to:
•
To describe the translational aspects of and issues involved with, all types of cell and tissue-based research
•
To demonstrate cross-disciplinary participation from scientists, clinicians, laboratory personnel, regulatory
professionals, and others from both academia and industry
•
To identify the scientific, clinical, laboratory, and regulatory issues related to each type of cell-based research/therapy
•
To translate information and experience from more mature cellular research areas such as hematopoietic stem cell
transplantation to other emerging areas including non-hematopoietic areas such as mesenchymal stem cells, islet
cells, ESC’s, etc
•
To initiate the transfer of information and experience from senior practitioners to young scientists in the field
Faculty (For CME-Approved plenary Sessions)
continuing education
Walter Bodmer, PhD, FRCPath, FRS - University of Oxford - Weatherall Institute of Molecular Medicine, United Kingdom
Marc Dahlke, MD, PhD - University of Regensburg, Germany
Stefanie Dimmeler, PhD - University of Frankfurt, Germany
Elaine Dzierzak, PhD - Erasmus MC Stem Cell Institute, The Netherlands
Takumi Era, MD, PhD - Kumamoto University - Institute of Molecular Embryology and Genetics, Japan
Fred Falkenburg, MD, PhD - Leiden University Medical Center, The Netherlands
Anthony Hollander, PhD - University of Bristol, United Kingdom
Edwin Horwitz, MD, PhD - Children’s Hospital of Philadelphia, USA
Armand Keating, MD, FRCP(C) - Princess Margaret Hospital, Canada
Calvin Kuo, MD, PhD - Stanford University School of Medicine, USA
Karl-Ludwig Laugwitz, MD - University of Munich, Germany
Douglas Losordo, MD - Feinberg Cardiovascular Research Institute, USA
Matthias Lutolf, PhD - École Polytechnique Fédérale Lausanne, Switzerland
Ivan Martin, PhD - University Hospital Basel, Switzerland
Emma Morris, MA, PhD, MRCP, FRCPath - University College London Hospital, United Kingdom
Ton Schumacher, PhD - The Netherlands Cancer Institute, The Netherlands
Luc Sensebé, MD, PhD - Etablissement Français Du Sang EFS, France
Marc van de Wetering, PhD - Hubrecht Institute, The Netherlands
Catherine Verfaillie, MD - Katholieke Universiteit Leuven, Belgium
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Accreditation Statement
This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council
for Continuing Medical Education through the joint sponsorship of Postgraduate Institute for Medicine and The International
Society for Cellular Therapy. The Postgraduate Institute for Medicine is accredited by the ACCME to provide continuing medical
education for physicians.
Credit Designation
The Postgraduate Institute for Medicine designates this live activity for a maximum of 9 AMA PRA Category 1 Credit(s)™.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Disclosure of Conflicts of Interest
Postgraduate Institute for Medicine (PIM) assesses conflict of interest with its instructors, planners, managers and other individuals
who are in a position to control the content of CME activities. All relevant conflicts of interest that are identified are thoroughly
vetted by PIM for fair balance, scientific objectivity of studies utilized in this activity, and patient care recommendations. PIM is
committed to providing its learners with high quality CME activities and related materials that promote improvements or quality
in healthcare and not a specific proprietary business interest of a commercial interest.
Please refer to the inserted leaflet for reported financial relationships
The planners and managers reported the following financial relationships or relationships to products or devices they or their
spouse/life partner have with commercial interests related to the content of this CME activity:
The following PIM planners and managers, Jan Hixon, RN, BSN, MA, Trace Hutchison, PharmD, Julia Kimball, RN, BSN,
Samantha Mattiucci, PharmD, Jan Schultz, RN, MSN, CCMEP, and Patricia Staples, MSN, NP-C, CCRN hereby state that they
or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial
interest related to the content of this activity of any amount during the past 12 months.
Method of Participation and Request for Credit
continuing education
There are no fees for participating and receiving CME credit for this activity. During the period from May 19-21, 2011,
participants must read the learning objectives and faculty disclosures and study the educational activity.
4
PIM supports Green CME by offering your Request for Credit online. If you wish to receive acknowledgment for completing
this activity, please complete the post-test and evaluation on www.cmeuniversity.com. On the navigation menu, click on “Find
Post-test/Evaluation by Course” and search by course ID <8000>. Upon registering and successfully completing the post-test
with a score of 70% or better and the activity evaluation, your certificate will be made available immediately. Processing credit
requests online will reduce the amount of paper used by nearly 100,000 sheets per year.
Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the
FDA, EMA, or other regulatory bodies. PIM and The International Society for Cellular Therapy do not recommend the use of
any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of PIM
and The International Society for Cellular Therapy. Please refer to the official prescribing information for each product for
discussion of approved indications, contraindications, and warnings.
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their
own professional development. The information presented in this activity is not meant to serve as a guideline for patient
management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity
should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in
use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
Commercial Support Information
This program is supported by an unrestricted educational grant from Amgen Inc.
CMLE
This continuing medical laboratory education activity is recognized by the American Society for Clinical Pathology as meeting the
criteria for 20.25 hours of CMLE credit. ASCP CMLE credit hours are acceptable to meet the continuing education requirement
for the ASCP Board of Registry Certification Maintenance Program. California CMLE credits are also available for 20.25 hours.
Method of Participation and Request for Credit
There are no fees for participating and receiving CMLE credit for this activity. CMLE credits are offered for all Plenary Sessions,
Technical Sessions, Workshops, Technical Applications Track Sessions, Strategies for Commercialization Track Sessions and Oral
Presentation Sessions from May 19-21 of the program.
In order to receive credit for this activity, participants must complete the evaluations for the sessions they attend. The evaluation
booklet for CMLE is available at the registration desk. Alternatively, you may opt to complete the evaluation online (please
visit www.celltherapy2011.com). With the booklet, please ensure that you complete the first page of so that in the event your
booklet is found, we can return it to you. At the end of the meeting, you must return the evaluation booklet to the registration
desk. Online evaluation must be completed by June 17, 2011.
CMLE certificates will be sent by email within 6-7 weeks of the program end date.
continuing education
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Organizing Committee
Co-Chairs:
Ineke Slaper-Cortenbach, PhD
University Medical Center Utrecht, The Netherlands
Massimo Dominici, MD
University of Modena, Italy
Fred Falkenburg, MD, PhD
Leiden University Medical Center, The Netherlands
Members:
Bruce Levine, PhD
University of Pennsylvania, USA
Lizette Caballero, BSc, MT (ASCP)
Florida Hospital Cancer Institute, USA
Cor Lamers, PhD
Erasmus MC - Daniel Den Hoed Cancer Center,
The Netherlands
Tracey Lodie, PhD
Genzyme Corporation, USA
Technical Applications
Track Subcommittee
Strategies for Commercialization
Track Subcommittee
organizating committee
Chair: Chair:
6
Lizette Caballero, BSc, MT (ASCP)
Florida Hospital Cancer Institute, USA
Tracey Lodie, PhD
Genzyme Corporation, USA
Members: Members:
Elona Baum, JD
California Institute for Regenerative Medicine, USA
Dawn Driscoll, MB, MBA, PhD
DCi Biotech Inc, USA
Federico Rodriguez, MT, (ASCP), SBB
Yuma Regional Medical Center, USA
Jon Rowley, PhD
Lonza, USA
Karen Edward, BSc, MT(ASCP)
Advanced Cell & Gene Therapy, USA
Scott Burger, MD
Advanced Cell & Gene Therapy, USA
Kasper Westinga, BSc
UMC-Utrecht: Cell & Gene Therapy Facility, The Netherlands
Tara Clark, BSc
Miltenyi Biotec, USA
Martin Hildebrandt, MD
Hannover Medical School, Germany
Varda Deutsch, PhD
Tel-Aviv Sourasky Medical Center, Israel
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Invited Speakers and Chairs
Jeffrey Gimble, MD, PhD, Pennington Biomedical
Research Center, USA
Rosaria Giordano, MD, Fondazione Ospedale
Maggiore Policlinico, Italy
Janet Glassford, PhD, MHRA, UK
Frida Grynspan, PhD, Pluristem Therapeutics Inc., Israel
Ryan Guest, PhD, University of Manchester, UK
Mariann Gyöngyösi, MD, PhD, FESC, Medical University
of Vienna, Austria
Ian Harris, PhD, Stem Cell Organization of J&J
Biotechnology Center of Excellence, USA
Derek Hart, PhD, University of Sydney, Australia
Lyn Healy, PhD, National Institute for Biological Standards
and Control, UK
Martin Hildebrandt, MD, Hannover Medical School, Germany
Anthony Hollander, PhD, University of Bristol, UK
Edwin Horwitz, MD, PhD, Children’s Hospital of Philadelphia, USA
Ruud Hulspas, PhD, Cytonome/ST, LLC, USA
Martino Introna, MD, Laboratorio Di Terapia Cellulare E Genica, Italy
Zsuzsanna Izsvák, PhD, Max-Delbrück-Center for
Molecular Medicine (MDC), Germany
David James, Invetech, Australia
Sam Janes, MD, University College of London, UK
Inge Jedema, PhD, Leiden University Medical Center,
The Netherlands
Andrea Jochheim-Richter, Dr. rer. nat, Jochheim GMP
Consulting, Germany
Armand Keating, MD, FRCP(C), Princess Margaret Hospital, Canada
Kilian Kelly, PhD, Mesoblast, Australia
Ulrike Koehl, PhD, University Hospital Frankfurt, Germany
Calvin Kuo, MD, PhD, Stanford University School of Medicine, USA
Joanne Kurtzberg, MD, Duke University Medical Center, USA
Gunnar Kvalheim, MD, PhD, The Norwegian Radium
Hospital, Norway
Cor Lamers, PhD, Erasmus MC - Daniel Den Hoed Cancer Center,
The Netherlands
Francesco Lanza, MD, Hospital of Cremona, Italy
Karl-Ludwig Laugwitz, MD, University of Munich, Germany
Philippe Leboulch, MD, University of Paris, France
Bruce Levine, PhD, University of Pennsylvania, USA
Howard Levine, PhD, BioProcess Technology Consultants
Tracey Lodie, PhD, Genzyme Corporation, USA
Douglas Losordo, MD, Feinberg Cardiovascular Research
Institute, USA
Matthias Lutolf, PhD, École Polytechnique Fédérale
Lausanne, Switzerland
INVITED SPEAKERS AND CHAIRS
Stewart Abbot, PhD, Celgene Corporation, USA
Paul Anderson, Orthocell Pty Ltd., Australia
Lubomir Arseniev, MD, PhD, MBA, Cytonet
Hannover GmbH, Germany
Fouad Atouf, PhD, U.S. Pharmacopeia, USA
John Barrett, PhD, NIH NHLBI, USA
Ronnda Bartel, PhD, Aastrom Biosciences Inc., USA
Shirley Bartido, PhD, Memorial Sloan Kettering
Cancer Center, USA
Sven Becker, PhD, Becker GMP Consulting, Germany
Walter Bodmer, PhD, FRCPath, FRS, University of Oxford Weatherall Institute of Molecular Medicine, UK
Anthony Boitano, PhD, Genomics Institute of the
Novartis Research Foundation, USA
Catherine Bollard, MD, FRCPC, Baylor College of Medicine, USA
Mark Bonyhadi, PhD, Life Technologies, USA
Christopher Bravery, PhD, Consulting on Advanced Biologicals Ltd, UK
Scott Burger, MD, Advanced Cell & Gene Therapy, USA
Lizette Caballero, BSc, MT, Florida Hospital Cancer Institute, USA
Boris Calmels, PharmD, PhD, Institut Paoli Calmettes, France
Giovanna Cameron, RT, BC Cancer Research Centre, Canada
Miguel Carrion, MS, Lonza Walkersville, USA
Louis Casteilla, PhD, Université de Toulouse , France
Christian Chabannon, MD, PhD, Institut Paoli Calmettes, France
Marc Dahlke, MD, PhD, University of Regensburg, Germany
Christian Dani, PhD, University of Nice-Sophia Antipolis, France
Anthony Davies, PhD, Geron Corporation, USA
James Lawford Davies, Lawford Davies Denoon, UK
Jan De Boer, PhD, University of Twente, The Netherlands
Philip De Vries, MSc, UMC-Utrecht: Cell & Gene Therapy Facility,
The Netherlands
Alexander Denoon, Lawford Davies Denoon, UK
Varda Deutsch, PhD, Tel-Aviv Sourasky Medical Center, Israel
Stefanie Dimmeler, PhD, University of Frankfurt, Germany
Massimo Dominici, MD, University of Modena, Italy
Luc Douay, MD, PhD, Universite Pierre et Marie Curie, France
Rosemary Drake, PhD, The Automation Partnership, UK
Dawn Driscoll, MB, MBA, PhD, DCi Biotech Inc., Australia
Elaine Dzierzak, PhD, Erasmus MC Stem Cell Institute,
The Netherlands
Takumi Era, MD, PhD, Kumamoto University - Institute of
Molecular Embryology and Genetics, Japan
Fred Falkenburg, MD, PhD, Leiden University Medical Center,
The Netherlands
Sabine Fuchs, MS, PhD, Johannes Gutenberg University, Germany
Jacques Galipeau, MD, Emory University, USA
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INVITED SPEAKERS AND CHAIRS
Annual
Meeting
Paolo Madeddu, MD, University of Bristol, UK
Alejandro Madrigal, MD, PhD, FRCP, FRCPath, DSc, The Royal
Free and University College Medical School, UK
Frank Marini, PhD, MD Anderson Cancer Center, USA
Ivan Martin, PhD, University Hospital Basel, Switzerland
Simon Mauch, PhD, Miltenyi Biotec GmbH, Germany
Harald Mikkers, PhD, Leiden University Medical Center,
The Netherlands
Monica Moro, PhD, Istituto Nazionale di Genetica
Molecolare, Italy
Emma Morris, MA, PhD, MRCP, FRCPath, University College
London Hospital, UK
Natalie Mount, PhD, Pfizer Regenerative Medicine, UK
Arnon Nagler, MSc, MD, The Chaim Sheba Medical Center, Israel
Lynn O’Donnell, PhD, James Cancer Hospital &
Research Institute, USA
Hervé Petite, PhD, Université Paris Diderot, France
Anne Plant, PhD, National Institute of Standards
and Technology, USA
Frank Preijers, PhD, Radboud University Nijmegen
Medical Centre, The Netherlands
Shamim Rahman, PhD, Medizinische Hochschule
Hannover, Germany
Axel Rethwilm, PhD, University of Würzburg, Germany
Jon Rowley, PhD, Lonza Walkersville, USA
Marianna Sabatino, MD, National Institute of Health, USA
Ralf Sanzenbacher, PhD, Paul Ehrlich Institut, Germany
Delores Schendel, PhD, Institute of Molecular
Immunology, Germany
Ton Schumacher, PhD, The Netherlands Cancer Institute,
The Netherlands
Luc Sensebé, MD, PhD, Etablissement Français
Du Sang EFS, France
Ineke Slaper-Cortenbach, PhD, University Medical Center
Utrecht, The Netherlands
Jean Stanton, MSc, Johnson & Johnson, USA
Marc van de Wetering, PhD, Hubrecht Institute, The Netherlands
Gerjo van Osch, PhD, Erasmus MC, The Netherlands
Wouter Van’t Hoff, PhD, Athersys Inc., USA
Catherine Verfaillie, MD, Katholieke Universiteit Leuven, Belgium
Heike Walles, PhD, University of Würzburg, Germany
Daniel Weiss, MD, PhD, University of Vermont College of
Medicine, USA
Kasper Westinga, BSc, UMC-Utrecht: Cell & Gene Therapy
Facility, The Netherlands
Erik Woods, PhD, General BioTechnology, LLC, USA
ORAL PRESENTERS
Oral Presenters
8
Paul Anderson, Orthocell Pty Ltd., Australia
Cornelis A.M. van Bergen, Leiden University Medical Center,
The Netherlands
Zwi Berneman, MD, PhD, Antwerpuniversity Hospital, Belgium
Andrea Brennan, MSc, University of Pennsylvania, USA
Vanessa Bourgeaux, PhD, ERYtech Pharma, France
Lizette Caballero, BSc, MT (ASCP), Florida Hospital Cancer
Institute, USA
Jessica Carmen, PhD, Lonza Walkersville, USA
Nathalie Chossat-Clerget, PhD, TxCell, France
Patrizia Danieli, Fondazione IRCCS Policlinico San Matteo, Italy
Varda Deutsch, PhD, Tel-Aviv Sourasky Medical Center, Israel
Al Dietz, PhD, Mayo Foundation, USA
Martin Giedlin, PhD, Sangamo BioSciences, Inc., USA
Friederike Gieseke, PhD, Kinderkrebs-Zentrum Hamburg, Germany
Olivier Giet, PhD, University Hospital of Liege (BE), Belgium
Kenneth Harris, MSc, TotipotentSC, USA
Brooke Helfer, PhD, Celsense Inc, USA
Edwin Horwitz, MD, PhD, Children’s Hospital of Philadelphia, USA
Anna Janowska-Wieczorek, PhD, University of Alberta, Canada
Jean-Pierre Karam, PhD, INSERM, University of Angers, France
Morris Kletzel, MD, Children’s Memorial Hospital, USA
Cor Lamers, PhD, Erasmus MC - Daniel Den Hoed Cancer Center,
The Netherlands
Bruce Levine, PhD, University of Pennsylvania, USA
Yeh-ching Linn, MD, SIngapore General Hospital ,Singapore
Frank Marini, PhD, MD Anderson Cancer Center, USA
Benedetta Mazzanti PhD, Azienda Ospedaliero Universitaria
Careggi, Italy
Jaroslav Michalek, MD, Masaryk University, Czech Republic
Gustavo Moviglia, MD, Universidad Maimonides, Argentina
Nicole Prokopishyn, PhD, Calgary Laboratory Services, Canada
Anastasia Papadopoulou, PhD, G. Papanicolaou Hospital, Greece
Ineke Slaper-Cortenbach, PhD, Cell and Gene Therapy Facility
University Medical Center Utrecht, The Netherlands
Bert Wognum, PhD, STEMCELL Technologies Inc. Canada
Christodoulos Xinaris, PhD, Mario Negri Institute of
Pharmacological Research, Italy
Zhaohui Zheng, MSc, University of Pennsylvania, USA
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Wednesday May 18, 2011
(Pre-Conference Day)
7:00am – 7:00pm
Registration 8:00am – 5:00pm
Global Regulatory Perspectives Workshop
– separate registration fee required
9:00am – 6:15pm
Willem Burger Hall
Jurriaanse Zaal
FACT/JACIE Cellular Therapy Workshop – separate registration fee required
Fortis Bank Zaal
FACT/JACIE Cellular Therapy Workshop Breakout Session – separate registration fee required
Plate Zaal/Van der Vorm Zaal
2:30pm – 4:30pm
Corporate Symposium – BD Biosciences (Refer to Corporate Conference Guide for details)
Willem Burger Zaal
5:00pm – 7:00pm
Corporate Symposium – Miltenyi Biotec GmbH (Refer to Corporate Conference Guide for details)
Willem Burger Zaal
7:00pm – 9:30pm
Exhibits Open 7:00pm – 7:30pm
Welcome Address
7:30pm – 9:30pm
Welcome Reception in Exhibit Hall Arcadis /Van de Mandele /Jurriaanse Foyer
Jurriaanse Zaal
Arcadis /Van de Mandele /Jurriaanse Foyer
Thursday May 19, 2011
7:00am – 4:00pm
Registration
Willem Burger Hall
Technical Session 1
Imaging Cell Therapy
Jurriaanse Zaal
Chair: Hervé Petite (France)
Speakers:
Hervé Petite (France) – Use of bioluminescence imaging for monitoring mesenchymal stem cell survival r
Mariann Gyöngyösi (Austria) – Non-invasive tracking of the cardially injected stem cell
Technical Session 2
Practical Considerations in Cell Selection for Cellular Therapy Plate Zaal/Van der Vorm Zaal
Chair: Ruud Hulspas (USA)
Speakers:
Bruce Levine (USA) – Aspects of magnetic and centrifugal-based cell sorting for clinical trials
Ruud Hulspas (USA) – Practical Considerations in Cell Selection for Cellular Therapy
7:45am – 8:45am
Strategies for Commercialization Track 1
Positioning for Phase III Manufacturing Fortis Bank Zaal
Chair: Ian Harris (USA)
Speakers:
Ian Harris (USA) – What is needed for the manufacture of pivotal batches of cell based products
Wouter van’t Hoff (USA) – Characterization and potency assay development for MultiStem: An adult bone marrow derived adherent
stem cell therapy product
Technical Applications Track 1
Quality and Technical Agreements for Cell Therapy Facilities
Van Rijckevorsel/Ruys Zaal
Chair: Shirley Bartido (USA)
Speakers:
Shirley Bartido (USA) – Quality and Technical Agreements for Cell Therapy Facilities
Andrea Jochheim-Richter (Germany) – Quality and Technical Agreements for Cell Therapy Facilities
Plenary Session 1 – Presidential Plenary on Mesenchymal Stem Cells
10:30am – 11:00am
Coffee Break with Exhibits
Willem Burger Zaal
program
9:00am – 10:30am
Chair: Ed Horwitz (USA)
Speakers:
Armand Keating (Canada) – MSCs: Current Clinical Applications and Future Challenges
Luc Sensebé (France) – MSC from genetic stability to controls of safety
Marc Dalhke (Germany) – MISOT – Mesenchymal Stem Cells in Solid Organ Transplantation
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Oral Abstract Presentations 1 – Regenerative Medicine and Tissue Engineering
Co-Chairs: Ineke Slaper-Cortenbach (The Netherlands) and Ivan Martin (Switzerland)
Willem Burger Zaal
Inositol Hexaphosphate-Loaded Red Blood Cells As Preventive therapy in Sickle Cell Disease (Abstract # 1)
Speaker: Vanessa Bourgeaux (France)
24 hr Bone Tissue Formation using Mesenquimal Stem Cells Combined with Effector T Cells and Platelet Enriched Plasma
on a Matrix of Hydroxyapatite. Feasibility and Animal Proof of Principles. (Abstract # 2)
Speaker: Gustavo Moviglia (Argentina)
Autologous Tenocyte injection (Ati) For the Treatment of Lateral Epicondylitis: Phase I/II Study in Perth (Abstract # 3)
Speaker: Paul Anderson (USA)
Intramuscolar injection of Mesenchymal Stromal Cells in A Preclinical Model of Lower Esophageal Sphincter injury
(Abstract # 4)
Speaker: Benedetta Mazzanti (Italy)
Development of Pharmacologically Active Microcarriers Transporting Stem Cells and Releasing Growth Factors For
Cardiac Stem Cell Regeneration (Abstract # 5)
Speaker: Jean-Pierre Karam (France)
Oral Abstract Presentations 2 – Hematopoietic Stem Cells
Co-Chairs: Fred Falkenburg (The Netherlands) and Christian Chabannon (France)
Jurriaanse Zaal
19F Mri Cellular Tracer Preserves the Differentiation Potential of Hematopoietic Stem Cells (Abstract # 6)
Speaker: Brooke Helfer (USA)
Automation of the Colony-Forming Cell Assay For Measuring Hematopoietic Progenitors in Cord Blood (Abstract # 7)
Speaker: Bert Wognum (Canada)
MT1-MMP Is involved in the Mobilization and Homing of Hematopoietic Stem/Progenitor Cells (Abstract # 8)
Speaker: Anna Janowska-Wieczorek (Canada)
11:00am – 12:15pm
High Definition Flow Cytometry Markers Provide Clear Resolution of Different Hsc and Mk-P Populations and their
Subsets in Normal and Disease States (Abstract # 9)
Speaker: Varda Deutsch (Israel)
Oral Abstract Presentations 3 – Laboratory Practices/Legal & Regulatory Affairs
Co-Chair: Martino Introna (Italy) and Martin Hildebrandt (Germany) Van Rijckevorsel/Ruys Zaal
Implementing ISBT 128 Standards as a Traceability Tool in a Cellular Therapy Facility: the Experience of the Ulice
Program (2006-2010) (Abstract # 11)
Speaker: Olivier Giet (Belgium)
Comparison and Validation of Chimerism in Pediatrics Recipients of Hematopoietic Stem Cell Transplantation (Hsct) A
Comparison Between Two Methods: Real-Time Pcr (Qrt-Pcr) Vs. Variable Number Tandem Repeats (VNTR) (Abstract # 12)
Speaker: Morris Kletzel (USA)
Post Thaw Cd34 Recovery and Viability of Hematopoietic Progenitor Cells Using A Simplified Dilution Method and a
Modified Gating and Analysis Strategy (Abstract # 13)
Speaker: Nicole Prokopishyn (Canada)
Development of A Process to Determine the Effect of Dmso On Microbiology Culture Samples (Abstract # 14)
Speaker: Lizette Caballero (USA)
Conducting Affordable Cell Therapy Clinical Trials in India - Competency of the Cro to meet Regulatory Guidelines
(Abstract # 15)
Speaker: Kenneth Harris (USA)
Strategies for Commercialization Track 2
Cell Characterization, Potency, and Comparability Studies
Fortis Bank Zaal
Chair: Scott Burger (USA)
Speakers:
Scott Burger (USA) – US FDA Expectations for Cell Therapy Potency Testing
Janet Glassford (UK) – Potency Assays for Cell Therapies: A European Regulator’s Perspective
Anne Plant (USA) – Assurance in Cell Measurements
program
12:15pm – 1:45pm
10
12:30pm – 1:30pm
Lunch with Exhibits
Fortis Bank Zaal
Corporate Tutorial – BioLife Solutions Inc. (Refer to Corporate Conference Guide for details)
Fortis Bank Zaal
Corporate Tutorial - Thermo Scientific (Refer to Corporate Conference Guide for details)
Plenary Session 2 – Regenerative Medicine and Tissue Engineering 1:45pm – 3:15pm
Chair: Ivan Martin (Switzerland)
Speakers:
Anthony Hollander (UK) – Cartilage tissue engineering: are we ready to translate into the clinic?
Ivan Martin (Switzerland) – Challenges in 3D tissue graft manufacturing
Matthias Lutolf (Switzerland) – Smart materials for programming stem cell fate in situ
Jurriaanse Zaal
Willem Burger Zaal
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
3:15pm – 3:30pm
Coffee Break with Exhibits
Workshop 1
Ex-Vivo Expansion (Joint Session with EBMT)
Willem Burger Zaal
Co-Chairs: Christian Chabannon (France), Alejandro Madrigal (UK)
Speakers:
Luc Douay (France) – From Stem Cells to Red Blood Cells in vitro: Perspectives for Transfusion Medicine
Anthony Boitano (USA) – Aryl hydrocarbon receptor antagonists promote expansion of human hematopoietic stem cells
Arnon Nagler (Israel) – Novel strategies for ex vivo expansion of human umbilical cord blood for clinical transplantation
Workshop 2
Mesenchymal Stem/Stromal Cells and Tumors
Jurriaanse Zaal
Chair: Massimo Dominici (Italy)
Speakers:
Jacques Galipeau (USA) – MSCs Bite Back – MSCs as antigen presenting cells for cancer immunotherapy
Frank Marini (USA) – Mesenchymal stem/stromal cells: their role in tumor stroma development and as potent anti-cancer cellular vehicles
Massimo Dominici (Italy) – Transforming MSC from regenerative tools in killer cells for cancer: the Mesenkillers
Workshop 3
3:30pm – 5:00pm
Antigen Specific T Cells
Plate Zaal/Van der Vorm Zaal
Chair: Catherine Bollard (USA)
Speakers:
Catherine Bollard (USA) – Priming and Expanding Virus-Specific T Cells from Naïve Cord Blood
John Barrett (USA) – Approaches to Generating Leukemia Antigen Specific T Cells
Inge Jedema (The Netherlands) – Priming and Isolation of Virus and mHag-specific T Cells from Adult Naïve T Cell Compartments
Strategies for Commercialization Track 3
Advanced Automation for Autologous Processing Fortis Bank Zaal
Chair: Jon Rowley (USA)
Speakers:
Rosemary Drake (UK) – Challenges in ex-vivo expansion of cell therapy products and automated manufacturing
Simon Mauch (Germany) – Integrated automation for the development and manufacturing of cellular therapies
David James (Australia) – Automation is critical but only part of the solution
Technical Applications Track 2
Safety Testing for Cell Therapy Products: Requirements, Relevance, and New Technologies
Van Rijckevorsel/Ruys Zaal
Chair: Mark Bonyhadi (USA)
Speakers:
Scott Burger (USA) – Regulatory Requirements for Safety Testing
Marianna Sabatino (USA) – Determining if Mesenchymal Stromal Cells Have Passed (Passaged) Their Prime
Mark Bonyhadi (USA) – Technologies for Rapid Testing
5:00pm – 6:00pm
Poster Session 1
5:00pm – 7:30pm
Industry Community Networking Reception Invitation Only
6:00pm – 7:00pm
Lab Practices Committee Meeting
Willem Burger Hall
Van der Vorm/Plate Zaal
Fortis Bank Zaal
Friday May 20, 2011
7:00am – 4:00pm
Registration
Willem Burger Hall
Technical Session 3
Potency Assays in Stem Cell Based Therapeutics
7:30am – 8:30am
Jurriaanse Zaal
Chair: Rosaria Giordano (Italy)
Speakers:
Jan de Boer (The Netherlands) – An in vitro diagnostic marker for the efficacy of human MSC-based bone tissue engineering
Monica Moro (Italy) – How we can see them
Chair: Harald Mikkers (The Netherlands)
Speakers:
Harald Mikkers (The Netherlands) – iPS cells for treating blood disorders
Lyn Healy (UK) – Banking of hESC and iPS cell lines for research and clinical use
Plate Zaal/Van der Vorm Zaal
program
Technical Session 4
ES/iPS Cells
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Strategies for Commercialization Track 4
Risk Assessments
Fortis Bank Zaal
Chair: Christopher Bravery (UK)
Speakers:
Christopher Bravery (UK) – The EU risk-based approach: what does it mean?
Jean Stanton (USA) – Application of Quality Risk Management Tools for Cell Therapy Manufacturing
7:30am – 8:30am
Technical Applications Track 3
Environmental Monitoring: How much is enough
Van Rijckevorsel/Ruys Zaal
Chair: Kasper Westinga (The Netherlands)
Speaker:
Philip de Vries (The Netherlands) – Environmental Monitoring in a Dutch University Hospital GMP Production Facility
Lynn O’Donnell (USA) – Environmental Monitoring: How much is enough? A U.S. Perspective
Plenary Session 3 – Cardiovascular Cell Therapy
8:45am – 10:15am
10:15am –10:45am
Willem Burger Zaal
Chair: Stefanie Dimmeler (Germany)
Speakers:
Douglas Losordo (USA) – Repair by bone marrow-derived cells: experimental and clinical insights
Karl-Ludwig Laugwitz (Germany) – Human iPSC models of cardiac disease
Stefanie Dimmeler (Germany) – microRNAs in cardiovascular repair
Coffee Break with Exhibits
Oral Abstract Presentations 4 – Basic Biology of Non-Hematapoietic Stem Cells/NonWillem Burger Zaal
Hematapoietic Stem Cells towards the Clinic
Co-Chairs: Massimo Dominici (Italy) and Luc Sensebé (France)
A Novel Strategy to Enhance Mesenchymal Stem Cell Migration and Therapeutic Efficacy (Abstract # 16)
Speaker: Christodoulos Xinaris (Italy)
The Role of Cd44 in the Participation of Mesenchymal Stem/Stromal Cell (Msc) to the Tumor Microenvironment (Abstract # 17)
Speaker: Frank Marini (USA)
Tumour-Derived Stromal Cells Share Immunomodulatory Properties with Multipotent Mesenchymal Stromal Cells
(Abstract #18)
Speaker: Friederike Gieseke (Germany)
Treatment of Steroid Resistant Grade II to IV Acute GVHD By infusion of Mesenchymal Stromal Cells Expanded with
Platelet Lysate – A Phase I/II Study (Abstract # 19)
Speaker: Ineke Slaper-Cortenbach (The Netherlands)
Repeated infusions of Allogeneic Msc’s Maintain Accelerated Growth in Children with Severe Osteogenesis Imperfecta
(Abstract # 20)
Speaker: Ed Horwitz (USA)
A Short Pretreatment with Bortezomib Circumvents the Limitations of Mesenchymal Stem Cells’ in Vivo Performance,
Providing Significant Clinical Benefit in Experimental Arthritis (Abstract # 21)
10:45am – 12:15pm
Speaker: Anastasia Papadopoulou (Greece)
Oral Abstract Presentations 5 – Immunotherapy & Dendritic Cells
Co-Chairs: John Barrett (USA) and Derek Hart (Australia)
Jurriaanse Zaal
Multi-Center Clinical Trial of Adoptive Immunotherapy with Autologous Cd3/Cd28-Costimulated T-Cells After
Fludarabine-Based Chemotherapy in Patients with Chronic Lymphocytic Leukemia (Abstract # 22)
Speaker: Zhaohui Zheng (USA)
Dendritic Cell Vaccination in Leukemia and Aids: An Update (Abstract # 23)
Speaker: Zwi Berneman (Belgium)
Autologous Cellular therapy Open Label Phase I Study in Chronic Active Crohn’s Disease (Cacd) with Type 1 Regulatory
(Tr1) Lymphocytes (Cats1) (Abstract #24)
Speaker: Nathalie Chossat-Clerget (France)
Selective Graft Versus Leukemia Reactions After Donor Lymphocyte infusion Coincide with Minor Histocompatibility
Antigen Responses in Graft Versus Host Disease Free Patients (Abstract # 25)
program
Speaker: Cornelis A.M. van Bergen (The Netherlands)
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Allogeneic Cytokine-induced Killer Cells Demonstrate Anti-Tumour Activity in Patients Who Relapse After Allogeneic
Haemopoietic Stem Cell Transplant For Haematological Malignancies (Abstract # 26)
Speaker: Yeh-ching Linn (Singapore)
Tolerogenic Dendritic Cells For Type 1 Diabetes Immunotherapy (Abstract # 27)
Speaker: Jaroslav Michalek (Czech Republic)
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Strategies for Commercialization Track 5
Decreasing Corporate Risk for Cell Therapy Programs
Fortis Bank Zaal
Chair: Dawn Driscoll (Australia)
Speakers:
Natalie Mount (UK) -Using excellence in clinical program design to mitigate corporate risk for cell therapy products
David James (Australia) – The manufacturing investment dilemma
Paul Anderson (Australia) – Portfolio Diversification in Regenerative Medicine – Strategies for Decreasing Risk
10:45am – 12:15pm
Technical Applications Track 4
CD34 enumeration, how and when 2011
Van Rijckevorsel/Ruys Zaal
Chair: Varda Deutsch (Israel)
Speakers:
Frank Preijers (The Netherlands) – Prerequisites for a reliable CD34 determination
Joanne Kurtzberg (USA) – Enumeration of CD34 from fresh and cryopreserved human cord blood
Lubomir Arseniev (Germany) – Cellular quality control of haematopoietic grafts: regulatory environment, validation and justification of
chosen methods
12:15pm – 1:45pm
12:30pm – 1:30pm
Lunch with Exhibits
Annual General Meeting Van der Vorm/Plate Zaal
Corporate Tutorial – Biosafe SA (Refer to Corporate Conference Guide for details)
Corporate Tutorial – CellGenix GmbH & Afc (Refer to Corporate Conference Guide for details)
Plenary Session 4 – T Cell Immunotherapy
1:45pm – 3:15pm
3:15pm – 3:30pm
Willem Burger Zaal
Jurriaanse Zaal
Willem Burger Zaal
Chair: Fred Falkenburg (The Netherlands)
Speakers:
Fred Falkenburg (The Netherlands) – Alloreactive T cells for the treatment of leukemia
Ton Schumacher (The Netherlands) – Dissection of cell therapy-induced cytotoxic T cell responses in melanoma
Emma Morris (UK) – Translation of immunotherapy using WT-1 and CMV specific TCR gene transfer into the clinic
Coffee Break with Exhibits
Workshop 4
How to improve in vivo vascularisation (Joint Session with TERMIS-EU)
Willem Burger Zaal
Co-Chairs: Ineke Slaper-Cortenbach (The Netherlands), Gerjo van Osch (The Netherlands)
Speakers:
Gerjo van Osch (The Netherlands) – The importance of vascularisation and different ways to obtain vascularisation
Sabine Fuchs (Germany) – Neovascularization strategies in tissue engineering based on natural cell to cell interactions
Heike Walles (Germany) – The use of decellularized tissues to provide a scaffold for rapid vascularisation
Workshop 5
Dendritic Cells
Jurriaanse Zaal
Chair: Gunner Kvalheim (Norway)
Speakers:
Gunner Kvalheim (Norway) – DC vaccines targeting the tumors stem cells
Delores Schendel (Germany) – Young, TLR-activated DCs display optimal characteristics for vaccine use
Derek Hart (Australia) – Dendritic cell subsets and cross-presentation: the potential benefits of receptor targeted antigen loading
3:30pm – 5:00pm
Strategies for Commercialization Track 6
Challenges of Commercial Development of Pluripotent hES
Fortis Bank Zaal
Chair: Anthony Davies (USA)
Speakers:
Anthony Davies (USA) – Development of Human Embryonic Stem Cell-Derived Therapeutics Manufacturing to Support Future
Commercialization
James Lawford Davies (UK) and Alexander Denoon (UK) – Negotiating the Regulatory and IP Hurdles
Howard Levine (USA) – Challenges in the GMP manufacturing of pluripotent hES: Lessons learned from monoclonal antibodies
Technical Applications Track 5
program
Establishing GMP Facilities with QA Oversight in Academic Centers for Phase I/II Clinical Trials Van Rijckevorsel/Ruys Zaal
Co-Chairs: Shirley Bartido (USA), Martin Hildebrandt (Germany)
Speakers:
Shirley Bartido (USA) – GMP Facilities in US Academic Centers: their Trials and Tribulations
Martin Hildebrandt (Germany) – Academic GMP – Industry standards in a non-industry environment
Martino Introna (Italy) – Feasibility of a GMP Facility inside a Public Hospital in Italy
Sven Becker (Germany) – A surprisingly big step: from an academic scientist to a pharmaceutical entrepreneur
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5:00pm – 6:00pm
Poster Session 2
6:00pm – 11:00pm
Gala Event separate registration fee required
6:00pm – 7:30pm
Reception at Rotterdam City Hall
7:30pm – 11:00pm
Dinner, SS Rotterdam
Willem Burger Hall
Saturday May 21, 2011
7:00am – 3:00pm
Registration
Willem Burger Hall
Technical Session 5
Adipose Mesenchymal Progenitors
Jurriaanse Zaal
Chair: Louis Casteilla (France)
Speakers:
Louis Casteilla (France) – Isolation and Biology of Adipose derived stromal cells: comparison with bone marrow mesenchymal stem cells
Jeffrey Gimble (USA) – Adipose-derived cells: How does that translate?
Christian Dani (France) – Human adipocyte progenitors: Maintenance ex vivo and regulation of their self-renewal and differentiation
Technical Session 6
Ancillary Materials
7:30am – 8:30am
Plate Zaal/Van der Vorm Zaal
Chair: Fouad Atouf (USA)
Speakers:
Fouad Atouf (USA) – Ancillary Materials Used in Cell Manufacturing: Qualification Programs and Quality Attributes
Ralf Sanzenbacher (Germany) – Manufacture of Somatic Cell Therapy and Tissue-engineered Products: Considerations on Quality Aspects
Strategies for Commercialization Track 7
Personalized Approach to Cell and Gene Therapy
Fortis Bank Zaal
Chair: Philippe Leboulch (France)
Speakers:
Philippe Leboulch (France) – Lentiviral therapies for genetic disorders: illustration with adrenoleukodystrophy and the betahemoglobinopathies
Ronnda L. Bartel (USA) – Ixmyelocel-T - A New Therapy for Severe Chronic Cardiovascular Disease
Technical Applications Track 6
The Essentials of Validation, Qualification and Verification
Van Rijckevorsel/Ruys Zaal
Chair: Lizette Caballero (USA)
Speakers:
Lizette Caballero (USA) – Qualification and Validation of new freezing containers: our experience
Ulrike Koehl (Germany) – Validation and flow cytometric quality control for CD3/CD19 depleted grafts
Plenary Session 5 – Cancer Stem Cells
8:45am – 10:15am
10:15am – 10:45am
Willem Burger Zaal
Chair: Sir Walter Bodmer (UK)
Speakers:
Sir Walter Bodmer (UK) – Cancer stem cells from colorectal cancer cell lines
Marc van de Wetering (The Netherlands) – Lgr5 Intestinal Stem Cells in self-renewal and cancer
Calvin Kuo (USA) – Modeling Colon Stem Cells and Neoplasia Using Primary Explant Cultures Containing an Endogenous Wntdependent Niche
Coffee Break with Exhibits
Oral Abstract Presentations 6 – Cell and Gene therapy/Cellular Gene Transfer
Chair: Paolo Madeddu (UK) and Philippe Leboulch (France)
Willem Burger Zaal
Ccr5 Disrupted Cd4+ T Cells Can Be Consistently Manufactured At Clinical Scale From Hiv+ Patients with Suboptimal
Cd4+ Counts (250-500 Cells/mm3) (Abstract # 28)
Speaker: Martin Giedlin (USA)
program
Immune Responses to Transgene and Retroviral Vector in Patients Treated with Ex Vivo Engineered T-Cells (Abstract # 29)
14
10:45am – 11:45pm
Speaker: Cor Lamers (The Netherlands)
Clinical Scale Electroporation of T Cells with Rna Encoding a Chimeric Antigen Receptor (Car) Mediates Regression of
Human Metastatic Mesothelioma at a Fraction of the Cost and Regulatory Burden of Viral Vectors (Abstract # 30)
Speaker: Andrea Brennan (USA)
Redirected Autologous T Cells Engineered to Contain Anti-Cd19 Attached to TCRzeta and 4-1Bb Signaling Domains: in Vivo
Expansion, Persistence and Anti-Tumor Activity in Patients with Chemotherapy Resistant or Refractory Cll (Abstract # 31)
Speaker: Bruce Levine (USA)
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Oral Abstract Presentations 7 – Translational Process Development/ Cardiovascular
Regeneration
Chair: Tracey Lodie (USA) and Francesco Lanza (Italy)
Jurriaanse Zaal
From Concept to Patient Treatment: A Clinical Trial of Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis
(Abstract # 32)
Speaker: Allan Dietz (USA)
Cell Characterization: Developing Assays to Address the Biological Parameters of Identity and Potency (Abstract # 33)
Speaker: Jessica Carmen (USA)
10:45am – 11:45pm
Combined Transcriptomic and Proteomic Approach Identifies Several Putative Paracrine Factors of Fetal Mesenchymal
Stem Cells (Abstract # 35)
Speaker: Patrizia Danieli (Italy)
Technical Applications Track 7 Van Rijckevorsel/Ruys Zaal
ISBT 128 Labeling: We’ve implemented, and so can you! Chair: Ineke Slaper-Cortenbach (The Netherlands)
Speakers:
Boris Calmels (France) – Implementation of ISBT 128 through the development of an ISBT 128-compliant software for labeling CT products
Giovanna Cameron (Canada) – Implementing ISBT 128 for a Multisite BMT Program
11:45pm – 1:15pm
11:45am – 1:15pm
Lunch with Exhibits
Networking Session for Operations Specialists Fortis Bank Zaal
(See page 2 for more details)
Workshop 6
New Gene Transfer Technologies (Joint Session with ESGCT)
Willem Burger Zaal
Co-Chairs: Cor Lamers (The Netherlands), Paolo Madeddu (UK)
Speakers:
Zsuzsanna Izsvák (Germany) – Translating transposons into cellular therapies: victories and challenges
Shamim Rahman (Germany) – Cut & Paste – Designer Nucleases for Targeted Genome Editing
Axel Rethwilm (Germany) – New developments in viral gene transfer
Workshop 7
Lung Regeneration
Jurriaanse Zaal
Chair: Dan Weiss (USA)
Speakers:
Dan Weiss (USA) – Cell Therapy and Bioengineering Approaches for Lung Repair and Regeneration
Sam Janes (UK) – Cell Therapy for Lung Cancer and the Roadmap Ahead
1:15pm – 2:45pm
Strategies for Commercialization Track 8
Strategies for Allogeneic Cell Therapy Commercialization
Fortis Bank Zaal
Chair: Stewart Abbot (USA)
Speakers:
Kilian Kelly (Australia) – Commercialization of Allogeneic Mesenchymal Precursor Cells
Frida Grynspan (Israel) – Commercialization strategies for the development of PLX-PAD; placental expanded adherent stromal cells, an
“off the shelf” product
Technical Applications Track 8
Van Rijckevorsel/Ruys Zaal
Process Development: Optimization and qualification of processes for maintaining quality parameters of therapeutic cells
Chair: Jon Rowley (USA)
Speakers:
Miguel Carrion (USA) – Developing and transferring cell culture processes into manufacturing
Ryan Guest (UK) – Post-culture processing of a personalised cellular therapeutic product
Erik Woods (USA) – Packaging Considerations and Cryopreservation of Cell Therapy Products
2:45pm – 2:55pm
Break
Plenary Session 6 – Embryonic to Adult Stem Cells program
2:55pm - 4:25pm
Willem Burger Zaal
Chair: Elaine Dzierzak (The Netherlands)
Speakers:
Takumi Era (Japan) – Origin of mesenchymal stem cell
Elaine Dzierzak (The Netherlands) – the development of hematopoietic stem cells: Endothelial to hematopoietic transition
Catherine Verfaillie (Belgium)
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Plenary Session Synopses
Plenary Session 1
Presidential Plenary on Mesenchymal
Stem Cells
Thursday, May 19: Time: 9:00am - 10:30am
MSCs: Current Clinical Applications and
Future Challenges
Armand Keating
Presentation synopsis is available in the conference insert.
MSC from genetic stability to controls
of safety
plenary sessions
Luc Sensebé
16
In recent years, relevant data have indicated that mesenchymal
stromal/stem cells (MSC) can be used as reparative/
regenerative cells to treat a range of clinical conditions
including immunological disorders as well as degenerative
situations. A major safety concern is the genomic stability of
mesenchymal stromal cells particularly related to the risk of
cell transformation. As during ageing, cell expansion might
be associated with replicative senescence, replicative stress,
mutations, chromosomal abnormalities and other stochastic
cell defects that could progressively alter cells and have to be
investigated. Replicative senescence arises through different
well known mechanisms such as telomere shortening,
activation of pRB pathway through INK4a/ARF locus encoding
p16ink4a and p19ink4a, and activation of p53 pathway
(Krishnamurthy 2004, Campisi & d’Adda di Fagagna 2007).
As previously demonstrated MSCs transformation is a rare,
long, multistep process (Serakinci et al., 2004, Prockop et
al, 2010). Recently, we showed that clinical-grade–cultured
human MSCs, regardless of the presence of aneuploidy,
reached senescence and never transformed (Tarte et al.,
2010). However, the main control still used for the release
of GMP clinical grade MSC remains karyotype that appears
neither sufficient nor sensitive enough. To understand the
changes and risks induced by culture process, it is mandatory
to more deeply analyze genetic perturbations, not only the
main molecules of replicative senescence checkpoint (p53,
p21, p16, p19 and pRB) but also at a more subtle level
defective DNA replication program, which has been shown as
anticipating most gross cancer-associated genetic changes.
Molecular targets involved in genetic stability of MSC should
be defined to develop reliable quality controls for production
of safe MSC according to GMP.
• Campisi J & d’Adda di Fagagna F. Cellular senescence: when bad things happen
to good cells. Nat Rev Mol Cell Biol. 2007 ; 8 :729-740
• Krishnamurthy J, Torrice C, Ramsey M.R,Kovalev G.I, Al-Regaiey K, Su L, Sharpless
N.E. Ink4a/Arf expression is a biomarker of aging. J. Clin.Invest. 2004, 114:12991307
• Prockop DJ, Brenner M, Fibbe WE, Horwitz E, Le Blanc K, Phinney DG, Simmons
PJ, Sensebe L, Keating A (2010). Defining the risks of mesenchymal stromal cell
therapy. Cytotherapy 12:576-578
• Serakinci N, Guldberg P, Burns JS, Abdallah B, Schrodder H, Jensen T et al (2004).
Adult human mesenchymal stem cell as a target for neoplastic transformation.
Oncogene 23: 5095-8.
• Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H et al (2010).
Clinical-grade production of human mesenchymal stromal cells: occurrence of
aneuploidy without transformation. Blood 115: 1549-53.
MISOT - Mesenchymal Stem Cells in Solid
Organ Transplantation
Marc Dahlke
Solid organ transplantation provides the definitive
treatment for many end-stage diseases. However, lifelong immunosuppression needed to prevent graft rejection
causes clinically significant side effects. In fact, the overall
success of solid organ transplantation as a curative therapy
often depends on the occurrence and management of
drug side effects. Cellular immunomodulatory therapies
with MSC may therefore be suitable to reduce the dose of
immunosuppressive drugs.
The MISOT study group has brought European investigators
together and a variety of protocols to complement
immunosuppressive pharmacotherapy with MSC have
been suggested. To decide if patients undergoing organ
transplantation can be safely treated with MSC and if these
therapies yield a benefit for patient and graft survival, careful
consideration of all available preclinical and clinical data has
to be carried out.
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Plenary Session 2
Regenerative Medicine and Tissue Engineering
Thursday, May 19: Time: 1:45pm – 3:15pm
Cartilage tissue engineering: are we ready
to translate into the clinic?
Anthony Hollander
Tissue engineered cartilage may be used to treat degenerative
joint diseases such as osteoarthritis as well as diseases in
other cartilaginous structures such as the airway. Knowing
when we are ready to take our science out of the laboratory
and into the clinic is a key problem for the tissue engineer.
Articular cartilage repair using chondrocytes has been in
widespread use for 20 years but using stem cells to create
engineered cartilage that can be implanted into the joint
as a mature tissue has not yet been considered ready for
translation. Development of a more robust and predictable
outcome of cartilage tissue engineering may help to provide
the confidence need to use such implants therapeutically.
Meniscal cartilage repair has not received as much research
attention as articular cartilage and yet it is a significant
medical problem with no therapy available other than removal
of the torn tissue, resulting in a high risk of subsequent
osteoarthritis. Stem cells may provide a good opportunity
for a new approach to this old problem. Airway stenosis
does not affect large numbers of patients but it can be lifethreatening. Replacement of a severely damaged bronchus
with tissue engineered trachea in one patient has shown the
potential for whole organ replacement in the future. Each
of these examples will be considered as an illustration of the
complexity of knowing when we are ready to turn science
into medicine.
Challenges in 3D tissue graft
manufacturing
Despite the compelling clinical need to regenerate damaged
tissues/organs, impressive advances in the field of tissue
engineering have yet to result in viable engineered tissue
products with widespread therapeutic adoption. The main
challenges to be overcome have been identified in the yet
not convincing benefit of the proposed therapies, combined
with their high costs. Following the exemplifying paradigm
of bone and cartilage regeneration, the lecture will highlight
the bottlenecks of typical manufacturing strategies and will
propose alternative bioreactor-based approaches for the
manufacturing of 3D cellular grafts. The perspective will
Smart materials for programming stem
cell fate in situ
Matthias Lutolf
A complex mixture of extracellular cues delivered by support
cells is critical for adult stem cell maintenance and the
regulation of self-renewal in their microenvironment, termed
niche. Despite recent progress in the identification of relevant
niche proteins and signaling pathways in mice, to date, many
adult stem cell populations cannot be efficiently cultured in
vitro without rapidly differentiating.
In this talk I will highlight recent efforts in my lab to develop
and apply novel in vitro culture paradigms that allow fate
decisions of hundreds of individual adult stem cells to be
monitored under well-controlled conditions and in real time.
For example, we have engineered microarrayed ‘artificial
niches’ for hematopoietic stem cells (HSC) based on a
combination of biomolecular hydrogel and microfabrication
technologies that allow key biochemical characteristics of
niches to be mimicked and the physiological complexity
deconstructed into a smaller, experimentally amenable
number of distinct signaling interactions. We have also
built and applied microfluidic chips to sequentially capture
single HSC after multiple divisions to assess their fate, and in
particular the symmetry of division, by multigene single cell
qRT-PCR.
The systematic deconstruction of a stem cell niche may
serve as a broadly applicable paradigm for defining and
reconstructing artificial niches to accelerate the transition of
stem cell biology to the clinic.
plenary sessions
Ivan Martin
address issues related to quality standardization, process
control and regulatory compliance in manufacturing cellbased products and highlight the need not only to automate,
but also to streamline and simplify typical production
processes. Examples will be given on the attractive paradigm
to expand mesenchymal stem/progenitor cells from adult
individuals directly in a “3D niche” environment, thereby
maintaining a larger post-expansion differentiation capacity
and bypassing the complex and costly serial cell passaging
in monolayers. Finally, as a next generation paradigm, the
lecture will propose and exemplify the concept of engineering
regenerative strategies following principles of developmental
biology, using the own body as the in vivo bioreactor.
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Meeting
Plenary Session 3
Cardiovascular Cell Therapy
Friday, May 20: Time: 8:45am – 10:15am
Repair by bone marrow-derived cells:
experimental and clinical insights
Doug Losordo
Presentation synopsis is available in the conference insert.
Human iPSC models of cardiac disease
Karl-Ludwig Laugwitz
plenary sessions
Much of what is known about the molecular pathways
that lead to human cardiovascular disorders has come from
studying animal models, particularly genetically modified
mice. In some cases it is possible to translate genetic
discoveries from humans to mice (e.g. non-sense mutations),
but in most circumstances there are no direct correlates
for human genetic variants such as single nucleotide
polymorphisms (SNPs) or copy number variants. Therefore,
it is imperative to replicate relevant features of human
cardiovascular physiology in the context of the human
genome. Recent advances in stem cell biology now raise the
possibility of generating human models of cardiovascular
physiology and disease.
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Generating patient-specific cells and tissues has recently
emerged with the demonstration that exogenous expression
of four proteins in human skin fibroblasts (e.g. c-MYC, KLF4,
OCT4, and SOX2) is sufficient to induce pluripotency in the
cells. Although so-called induced pluripotent stem cells
(iPSCs) are not perfectly equivalent to human ES cells, they
retain important properties of ES cells such as the capacity
for long-term propagation and the ability to differentiate into
all human somatic cell types. Factor-based reprogramming
enables us of the long-standing ambitions of stem cell biology:
the ability to generate pluripotent cells from specific patients
and figuratively, move a patient`s disease into the Petri dish.
This will be discussed for human monogenetic cardiovascular
diseases, e.g. LQT syndromes, catecholaminergic polymorphic
ventricular tachycardia (CPVT) and arrhythmogenic right
ventricular dysplasia (ARVC).
Recent advances describing the derivation of human iPSCs
from peripheral, frozen blood brings the stem cell field an
important step closer to bio-banked blood samples and
eventual clinical use.
Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flügel L, Dorn T, Gödel A,
Höhnke C, Hofmann F, Seyfarth M, Sinnecker D, Schömig A & Laugwitz K-L (2010).
Patient-specific induced pluripotent stem cell models for long-QT syndrome. N Engl
J Med., Epub Jul 21.
microRNAs in cardiovascular repair
Stefanie Dimmeler
MicroRNAs (miRs) are small non-coding RNAs, which control
gene expression by either inducing mRNA degradation
or by blocking translation, and play a crucial role in tissue
homeostasis. In the cardiovascular system, miRs were shown
to control cardiac hypertrophy, fibrosis and apoptosis,
angiogenesis and vessel remodeling. In addition, miRs
regulate stem cell maintenance and some miRs induced cell
fate decisions. The presentation will provide an overview of
involvement of miRs in cardiovascular lineage commitment
and cell function. Particularly, the regulation and function
of miRs in bone marrow derived cells that are used for cell
therapy of cardiovascular diseases will be discussed.
Plenary Session 4
T Cell Immunotherapy
Friday, May 20: Time: 1:45pm – 3:15pm
Alloreactive T cells for the treatment of
leukemia
Fred Falkenburg
Allogeneic hematopoietic stem cell transplantation allows the
exploration of cellular immunotherapy strategies. Following
engraftment of donor hematopoiesis in the patient, donor
derived alloreactive T cells are capable of eliciting both graft
versus host disease (GVHD) and graft versus leukemia (GVL)
reactivity. Separation of immune responses resulting in GVHD
from those involved in GVL reactivity is essential for improving
the outcome of stem cell transplantation for hematological
disorders.
T cell responses directed against polymorphic antigens
expressed on normal non-hematopoietic tissues of the
recipient are likely to be responsible for severe GVHD. In
contrast, alloreactive donor derived T cell directed against
antigens preferentially expressed on cells of hematopoietic
origin may lead to profound reactivity against normal and
malignant hematopoietic cells of recipient origin while
preserving hematopoiesis of donor origin and sparing of
patient derived non-hematopoietic tissues thereby limiting
GVHD. Donor derived CD8 T cell responses directed against
antigens recognized in the context of HLA class-I molecules
will lead to strong cytotoxicity against target tissues. Since HLA
class-I molecules are broadly expressed on most tissues, only
CD8 T cells recognizing HLA class-I bound peptides derived
from hematopoiesis specific proteins have been considered
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
appropriate candidates for specific anti tumor reactivity after
transplantation. However, not all T cell reactivity against
antigens expressed on non hematopoietic tissues may lead
to severe GVHD. The cellular activation state influenced
by inflammatory circumstances in the non hematopoietic
tissues is an essential factor in the ability of T cells to damage
these tissues.
Since HLA class-II molecules show a more restricted tissue
distribution, T cell responses against antigens presented in
HLA class-II may also lead to relatively specific GVL responses.
T cell responses recognizing antigens in the context of HLADQ and HLA-DP have been found to be associated with anti
tumor effects with limited GVHD. However, inflammatory
circumstances in the recipient may lead to upregulation of
HLA class-II molecules on non-hematopoietic tissues resulting
in GVHD. These results illustrate that both the specificity of
the T cell responses, and the inflammatory environment will
determine the balance between GVHD and GVL reactivity
after allogeneic hematopoietic stem cell transplantation.
Dissection of cell therapy-induced cytotoxic
T cell responses in melanoma
Ton Schumacher
There is strong evidence that melanoma-reactive T cell
responses induced by immunotherapeutic interventions
such as anti-CTLA4 treatment or T cell therapy with tumorinfiltrating lymphocytes (TIL) can exert clinically meaningful
effects. However, at present we do not know which cytotoxic
T cell reactivities mediate cancer regression. Furthermore, as
the number of potential melanoma-associated antigens to
which these responses can be directed is very high, classical
strategies to map cytotoxic T cell reactivity do not suffice.
Knowledge of such reactivities would be useful to design
more targeted strategies that selectively aim to induce
immune reactivity against these antigens.
Translation of immunotherapy using WT1
and CMV specific TCR gene transfer into
the clinic
Emma Morris
Adoptive transfer of antigen-specific T cells is an effective
form of immunotherapy for persistent virus infections and
cancer. Major limitations of adoptive therapy are the inability
to isolate antigen-specific T cells reproducibly and expand
them to sufficient numbers ex vivo, whilst maintaining
optimal function and specificity.
We and others have developed gene therapy approaches
to overcome the problems related to poor tumour
immunogenicity and lack of specificity of allogeneic T cell
therapy. Retroviral gene transfer can generate large numbers
of high avidity antigen-specific T cells. Retroviral transfer of
cloned T cell receptor (TCR) genes reliably re-directs the antigen
specificity of T cells. We have exploited the allo-reactive T
cell repertoire to isolate high avidity T cells specific for the
tumour-associated antigen WT1, which is highly expressed
in MDS, AML, CML and ALL, together with a number of
solid tumours. The genes encoding the T cell receptor of the
WT1-specific, allo-restricted T cells were isolated and inserted
into retroviral vectors for gene transfer into primary human
T cells. In vitro, the gene modified T cells can kill primary
human leukaemia cells and also autologous leukaemia cells
expressing WT1 endogenously. Following adoptive transfer
they can protect against the growth of autologous primary
leukaemia cells in the xenogeneic NOD/SCID model. We can
now manufacture GMP grade WT1 TCR-transduced T cells
and aim to recruit patients into a Phase I study this year.
Reactivation of the latent human herpes virus,
Cytomegalovirus (CMV) post allogeneic haematopoietic
stem cell transplantation (Allo-HSCT) can result in significant
morbidity and mortality unless treated promptly. Anti-viral
therapy is usually effective, but has serious side effects, such as
myelosuppression (Ganciclovir) or nephrotoxicity (Foscarnet).
Cellular immunotherapy for CMV has been tested in Phase
I/II trials in the UK and Europe. In these trials CMV-specific
T cells were isolated from the peripheral blood of CMV
seropositive donors and re-infused into recipients following
CMV reactivation resulting in sustained anti-viral responses.
It is clear that post-transplant recovery of CD8+ CMV-specific
cytotoxic T-cells (CTL) abrogates the development of CMVrelated disease. An advantage of cellular therapy for CMV
reactivation is the transfer of immunological memory, which
can reduce the number of subsequent reactivations. We
have used TCR gene transfer to generate CMV pp65-specific
plenary sessions
In the past years we have aimed to address this issue
by designing MHC class I molecules occupied with UVsensitive ‘conditional’ peptide ligands, thereby allowing the
production of very large collections of pMHC complexes for T
cell detection. Secondly, we have developed a ‘combinatorial
coding’ strategy that allows the parallel detection of dozens
of different T cell populations within a single sample. The
combined use of MHC ligand exchange and combinatorial
coding allows the high-throughput dissection of diseaseand therapy-induced CTL immunity. We have now used
this platform to monitor immune reactivity against a panel
of over 200 melanoma-associated epitopes. Data on the
composition of TIL products used for adoptive cell therapy
and on the effect of TIL therapy on the tumor-reactive T cell
repertoire in melanoma patients will be presented.
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T cells from donors who are CMV seronegative (therefore
lack CMV-specific T cells), where the transplant recipient
is CMV seropositive and at risk of CMV reactivation post
transplant. Both CD8+ and CD4+ T cells expressing the MHC
class I-restricted TCR display CMV-specific effector function
in vitro and in vivo.
Plenary Session 5
Cancer Stem Cells
Saturday, May 21: Time: 8:45am – 10:15am
Cancer stem cells from colorectal cancer
cell lines
Sir Walter Bodmer
Colorectal cancer is one of the best defined cancers from
a genetic point of view, both at the germ line and somatic
levels. We work with a panel of more than 100 colorectal
cancer derived cell lines that are extensively characterised
with respect to their genetic/epigenetic make up and for
whole genome mRNA expression. The lines provide invaluable
models for studying the biology and somatic genetics of
colorectal cancers, and enable in vitro investigation of the
properties of colorectal cancer stem cells. We now can
characterise the driving cancer stem cells in these lines and
begin to identify the factors that control their differentiation,
in particular, through having shown that hypoxia(1% oxygen)
inhibits cancer stem cell differentiation in vitro.
Lgr5 Intestinal Stem Cells in self-renewal
and cancer
plenary sessions
Marc van de Wetering
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The intestinal epithelium is the most rapidly self-renewing tissue
in adult mammals. Current models state that 4-6 crypt stem cells
reside at the +4 position immediately above the Paneth cells
in the small intestine; colon stem cells remain undefined. Lgr5/
Gpr49 was selected from a panel of intestinal Wnt target genes
for its restricted crypt expression. Two knock-in alleles revealed
exclusive expression of Lgr5 in cycling, columnar cells at the
crypt base. In addition, Lgr5 was expressed in rare cells in several
other tissues. Using an inducible Cre knock-in allele and the
Rosa26-LacZ reporter strain, lineage tracing experiments were
performed in adult mice. The Lgr5+ve crypt base columnar cell
(CBC) generated all epithelial lineages over a 14 month period,
implying that it represents the stem cell of the small intestine
and colon. The expression pattern of Lgr5 suggests that it marks
stem cells in multiple adult tissues and cancers.
We have now established long-term culture conditions under
which single crypts undergo multiple crypt fission events, whilst
simultanously generating villus-like epithelial domains in which
all differentiated cell types are present. Single sorted Lgr5+ve
stem cells can also initiate these crypt-villus organoids. Tracing
experiments indicate that the Lgr5+ve stem cell hierarchy is
maintained in organoids. We conclude that intestinal crypt-villus
units are self-organizing structures, which can be built from a
single stem cell in the absence of a non-epithelial cellular niche.
Intestinal cancer is initiated by Wnt pathway-activating
mutations in genes such as APC. As in most cancers, the cell of
origin has remained elusive. Deletion of APC in in Lgr5+ve stem
cells leads to their transformation within days. Transformed
stem cells remain located at crypt bottoms, while fueling
a growing microadenoma. These microadenomas display
unimpeded growth and develop into macroscopic adenomas
within 4-6 weeks. When APC is deleted in short-lived Transit
Amplifying (TA) cells using a different Cre mouse, the growth of
the induced microadenomas rapidly stalls. Even after 30 weeks,
large adenomas are very rare in these mice. We conclude that
stem cell-specific loss of APC results in progressively growing
neoplasia. Moreover, a stem cell/progenitor cell hierarchy
is maintained in early stem cell-derived adenomas, lending
support to the “cancer stem cell”-concept.
Modeling Colon Stem Cells and Neoplasia
Using Primary Explant Cultures Containing
an Endogenous Wnt-dependent Niche
Calvin Kuo
The intestine undergoes continuous epithelial regeneration
that absolutely requires ongoing Wnt signaling. We have
developed in vitro culture systems that enable long-term
propagation and multi-lineage differentiation of intestinal
epithelium and allow sustained intestinal proliferation, multilineage differentiation and the support of Lgr5+ and Bmi1+
intestinal stem cells (ISC) over a range of 30 to > 350 d. The
defining characteristics of this approach include (1) culture
of intestinal epithelium within an air-liquid interface coupled
with a 3D culture matrix and (2) the use of explant tissue
that include stromal myofibroblasts, neural elements, and
recapitulate endogenous peristalsis. Notably, growth does
not require the addition of exogenous Wnt agonists, as
fetal calf serum alone is sufficient, and growth is ablated by
recombinant Dkk1, indicating the presence of endogenous
Wnt signaling within the explant cultures. This system
recapitulates both the cellular architecture and the rigorous
Wnt- and Notch- dependency of the intestinal stem cell
niche, and applications to the modeling of colon cancer will
be discussed.
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Plenary Session 6
Embryonic to Adult Stem Cells
Saturday, May 21: Time: 2:55pm – 4:25pm
Origin of mesenchymal stem cell
Takumi Era
Mesenchymal stem cell (MSC) is defined by their ability
both to undergo sustained proliferation in vitro and to give
rise to multiple mesenchymal cell lineages including bone,
cartilage, and fat cells. Although MSCs are a demonstrated
reality with applications in regenerative medicine, not
much is known about their in vivo characteristics, such as
their developmental derivation. Recently we found the
new the developmental pathway of MSC during mouse
embryogenesis. Using in vitro ES cell culture, we have shown
that Sox1+ neuroepithelial cells generate MSCs at the highest
efficiency. ES cell-derived day 9 PDGFRα+ precursors induced
by RA treatment morphologically exhibit fibroblastic and
undergo the self-renew in vitro with maintaining the potential
to give rise to multiple lineages including bone, cartilage,
and fat cells. Interestingly, the PDGFRα+ cells are derived
not from mesoderm cells but from neuroepithelium cells in
our ES cell culture. This unexpected result suggests that the
neuroepithelium is a candidate of embryonic origin of MSCs.
To confirm this result in actual embryo, we are proceeding to
search for the origin of MSCs in vivo using genetically fatetrucking method. In E9.5 embryos, we could induce MSCs
from Sox1+ cells but not from PDGFRα+ mesoderm. While
this type of MSC is found also in neonatal bone marrow at low
frequency, most MSCs in postnatal bone marrow are derived
from other origins, which are also enriched in the PDGFRα+
population. Thus, we show that MSCs are generated from
multiple sources, with those derived from neuroepithelium
constituting the earliest wave.
Elaine Dzierzak
Hematopoietic stem cells (HSC) are the source of all blood
cells in the adult. The first HSCs are generated in the aortagonad-mesonephros (AGM) region at midgestation in the
mouse embryo and at week 4-6 in human gestation. AGM
HSCs are generated following the anatomical appearance of
clusters of hematopoietic cells closely associated with the
lumenal wall of aorta and vitelline/umbilical arteries. The
relationship of HSCs to these clusters and the identification
of the precursors to HSCs is an area of intense research focus.
Please refer to conference Insert
Catherine Verfaillie
Presentation synopsis is available in the conference insert.
plenary sessions
The development of hematopoietic stem
cells: Endothelial to hematopoietic
transition
To begin to understand how clusters are formed we have
developed a 3-dimensional whole mount immunostaining
and confocal imaging method by which we can temporally
map and quantitate all hematopoietic clusters in normal (and
hematopoietic defective) mouse embryos (Yokomizo and
Dzierzak, Development, 2010). We have localized HSC activity
to the hematopoietic clusters. Visual proof that HSCs arise
from aortic endothelium comes from time lapse vital imaging
of the AGM (Boisset et al., Nature, 2010). Remarkably,
HSCs arise directly from endothelial cells of the dorsal aorta
in a natural transdifferentiation event. HSC generation is
regulated through ventral-derived developmental signals
and a group of pivotal (core) transcription factors, including
Runx1 and Gata2. Knockout strategies implicate these
factors in hematopoietic fate induction and/or expansion.
These transcription factors are required for the generation
of vascular hematopoietic clusters and HSCs. Developmental
signalling pathways triggered by BMP4 and Hedgehog,
appear to act upstream of these transcription factors.
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Technical Session Synopses
Technical Session 1
Imaging Cell Therapy
duration of the process), logistics, clinical grade antibodies,
sterility, controls, safety and regulatory requirements.
Thursday, May 19: Time: 7:45am - 8:45am
The possibility of isolating and expanding stem cells and of
driving them towards various phenotypes have motivated
exploration and development of stem cell based therapy.
In order to understand the mechanism, and to improve
the efficacy of these treatment approaches, the monitoring
of the fate and biodistribution of the transplanted cells is
necessary. The current non-invasive techniques of the in vivo
tracking of stem cells include direct labeling with magnetic
particles for magnet resonance imaging or radionuclides for
scintigraphic or positron emission computer tomography
(PET), and indirect labeling with reporter genes, such
as PET, fluorescence, or bioluminescence reporter gene
methods. The present session summarizes these techniques,
mentioning their particular advantages and usefulness under
experimental and clinical conditions in the context of bone
and cardiac tissue engineering.
Technical Session 2
Practical Considerations in Cell
Selection for Cellular Therapy
Technical sessions
Thursday, May 19: Time: 7:45am - 8:45am
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Cell selection methods for cellular therapy are generally first
optimized for use in small animal models. In most cases cell
selection involves magnetic particle cell sorting, high-speed
droplet sorting, or a combination of these two technologies.
Each technology requires optimized cell labeling protocols
to reliably obtain the cell population of interest. In
preparation for clinical trials these methods often need
changes to accommodate testing in humans. Moreover, the
increasingly complex phenotypic description of therapeutic
cell populations has made high-speed droplet sorting the cell
selection method of choice in many research settings. Highspeed droplet sorting in particular brings a series of challenges
when used in the clinic, presenting investigators with the
dilemma to either overcome the challenges or to switch to
magnetic particle cell sorting. This session is also intended to
facilitate sharing information about what works and what
doesn’t in cell selection methods for cellular therapy in the
clinic. Topics to discuss include: scaling up (antibody usage,
Technical Session 3
Potency Assays in Stem Cell Based Therapeutics
Friday, May 20: Time: 7:30am - 8:30am
A biological measurement of the activity of a cell product is
the most critical step in the product release for both clinical
trials as well as market-placed products.
The session will present you some intriguing applications of
two of the most popular techniques currently used for cell
product characterization: flow cytometry and microarray
analysis. Dr. de Boer will present a biopotency assay on
mesenchymal stromal cells used for bone tissue engineering.
In fact, large differences exist in bone forming efficacy
between MSCs isolated from different donors, but no proper
in vitro marker is known which predicts the in vivo bone
forming capacity of a given donor. He will present the use of
microarray analysis to correlate the in vitro gene expression
profile of MSCs of different donors with their potency to form
bone in an immune-deficient mouse model and identified
CadM1 as a highly predictive classifier. The presentation by
Dr. Moro will give you a general overview on how to use
flow-cytometry to identify the phenotypic characteristics that
corresponds to the target functional stem cell population.
Examples will be given in the context of hematopoietic as
well as mesenchymal stem cell applications.
Technical Session 4
ES/iPS Cells
Friday, May 20: Time: 7:30am - 8:30am
Two kinds of pluripotent stem cells exist, embryonic stem
(ES) cells and induced pluripotent stem (iPS) cells, which are
somatic cells that acquired pluripotency by the expression of
specific factors. Since these cells can be maintained in culture
indefinitely without losing the ability to generate all cell
types of a human body, they provide unique opportunities
to regenerative medicine, fundamental research and drug
or toxicity testing. In addition, the unlimited self-renewal
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
features allow the establishment of banks of pluripotent stem
cell lines covering most frequent haplotypes. In this session
an overview of the latest progress on the use of iPS cells for
treating blood disorders, and on the banking of pluripotent
stem cells for research and clinical purposes will be presented.
Technical Session 5
Adipose Mesenchymal Progenitors
Saturday, May 21: Time: 7:30am - 8:30am
The greatest interest of adipose tissue as a source of
therapeutic cells is the fact that there is no ethical concern
about this source since it is obtained from an adult, is
abundant and easy to get tissue, even when compared with
bone marrow, sampling of which requires more invasive
technique. Another advantage is that, as the frequency of
Adipose Derived Stromal Cells is much higher in adipose tissue
than those of MSC in bone marrow, a large number of cells
can be obtained without a large number of passages. In this
way, the risk of culture-induced chromosomal abnormality
senescence is largely decreased. On the other hand, a key
step in the process of isolation of adipose derived immature
cells is the digestion of the tissue and the choice of protocols
that can lead to isolate different cell subsets. This step and
the need of the adequate protocol for their in vitro culture
expansion is crucial for the security and the efficiency of
their therapeutic uses. This session deals with these different
points that represents a key stake for adult stem cell based
regenerative medicine.
Technical Session 6
Ancillary Materials
Saturday, May 21: Time: 7:30am - 8:30am
Quality of the components used in the manufacturing of
cellular or tissue-based therapies will have great impact
on the quality of finished products. Examples of these
components include the source cells and tissues, biomaterials,
ancillary materials, and excipients used in the formulation
of cellular or tissue-based therapies. Ancillary materials are
biological/biochemical substances which play an important
role in the manufacture of cellular therapies and also in the
manufacture of other therapeutics using living cells in their
processes. To ensure quality of finished goods, it is important
that qualification programs are in place, for the assessment
of these ancillary materials. The scope of this session is to
highlight the different quality aspects that relate to the
manufacture of somatic cell therapy and tissue-engineered
products, including a discussion on how the performance of
reagents can be evaluated through the use of materials with
acceptable test specifications.
Technical sessions
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Workshop Synopses
Workshop 1
Ex-Vivo Expansion (Joint Session with EBMT)
Workshop 3
Antigen Specific T Cells
Thursday, May 19: Time: 3:30pm - 5:00pm
Adoptive immunotherapy is emerging as a safe alternative to
chemotherapeutic drugs for both viral infections and relapsed
malignancies after hematopoietic stem cell transplantation
(SCT). Despite showing efficacy against virus infection in
numerous clinical trials, the lack of in vivo persistence of
transferred T cells and their unproven effectiveness against
various malignancies are challenges that have yet to be
overcome. To date, most if not all adoptively transferred
antigen-specific T cells have been derived from memory T
cells. Therefore, virus-specific T cells –though shown to
be effective for recipients of virus experienced donorsare unavailable for SCT recipients of cord blood or virusseronegative donor grafts. Pre-clinical data on human
antigen-specific T cells generated from naïve T cells has
been scant and mostly limited to EBV or OKT3-stimulated T
cells bearing exogenous TCRs. At this workshop session we
will now present novel developments (both preclinical and
clinical) demonstrating that antigen-specific T cells can be
generated from human naïve T cells using GMP compliant
technologies. In addition to viral infection, leukemic relapse
remains a significant cause of SCT treatment failure. Hence,
there is a need to develop additional strategies to enhance
the graft versus leukemia (GVL) effect. New approaches
to improve the GVL effect including vaccines to prime and
boost leukemia specific T cells and adoptive transfer of ex
vivo expanded leukemia specific cytotoxic T cells (CTL) will
also be discussed at this session.
Ex-vivo expansion represents the “Holy Grail” of stem cell
biologists, and a hope to improve results of human stem
cell transplantation, especially in situations where available
grafts contain limited numbers of hematopoietic progenitors,
such as in cord blood transplantation. Initial attempts mostly
relied on the use of cytokine combinations, but have largely
failed to produce clinically relevant results; the production of
differentiated, mature and functional cells may however be
feasible on a large scale and find applications within a near
future in selected situations. Next generations of pre-clinical and
clinical trials currently explore the possibility to manipulate other
types of signals that more directly regulate stem cell behavior
such as Notch. Recent results in murine models and in human
trials suggest that such targets can be identified, and that their
modulation can result in significant changes in hematopoietic
stem cell activity associated with potential clinical benefits
(enhanced hematopoietic recovery). The workshop will illustrate
some of the recent developments in this field.
Workshop 2
Mesenchymal Stem/Stromal Cells and Tumors
Thursday, May 19: Time: 3:30pm - 5:00pm
workshops
While large amount of data suggested the role of MSC as
regenerative tools by differentiation, new intriguing insights
are progressively indicating how these cells may be additionally
acting in releasing relevant amounts of largely unknown biomolecules to beused in different contexts of biomedicine.
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Based on this background this workshop will address how
wild type or gene modified MSC can be used as bio-molecules
factories against cancer mimicking immune effectors within
tumor stroma.
The speakers will here address the conflicting results on the
role of MSC in cancer in parallel suggesting the role of MSC
in inducing cancer death. The latest findings in the field will
be presented opening novel roles of MSC in oncology and
hematology.
Thursday, May 19: Time: 3:30pm - 5:00pm
Workshop 4
How to improve in vivo vascularisation
(Joint Session with TERMIS-EU)
Friday, May 20: Time: 3:30pm - 5:00pm
When a tissue engineered construct is implanted in the
body, survival of cells is a key point. Slow vascularisation of
the graft is one of the major problems. There are different
possible ways to improve vascularisation after implantation.
In this symposium different approaches to obtain rapid
vascularisation by engineering of new vessels in constructs
will be discussed. We will make use of an automatic
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
voting system and encourage discussion with challenging
statements to have the audience actively involved.
Includes a structured discussion at the end (approximately
30 minutes)
Workshop 5
Dendritic Cells
Friday, May 20: Time: 3:30pm - 5:00pm
Following Provenge’s FDA approval for DC vaccines on
prostate cancer there is again an increasing scientific interest
in clinical use of DC against cancer. Over the last 10 years
many centers around the world have been working with
DC vaccines. Most of these studies have been small nonrandomized studies treating patients with resistant metastatic
disease. Unfortunately, the success rate with DC vaccines has
been highly variable with clinical responses between 0-20%.
The reasons for these effects are multi-factorial and can not
be explained only by the type of patients offered DC vaccines.
This workshop will discuss which subtype of DC should be
used, how to mature the DC in vitro, which antigen should
be targeted in vivo, the route of administration of DCs, dose
of DCs, frequency and duration of DC vaccination. Finally
methods to break tolerance in vivo to improve clinical effects
of DC vaccination will also be discussed.
Workshop 7
Lung Regeneration
Saturday, May 21: Time: 1:15pm - 2:45pm
Many lung diseases remain incurable or have poor therapeutic
options. New approaches using both embryonic and
adult stem cells provide new potential therapeutic options
and are expected to be an area of rapid translational and
clinical growth. Following an overview of the current state
of the field, specific focus areas to be discussed will include
immunomodulation of lung diseases by mesenchymal
stromal cells (MSCs), clinical trials with MSCs and endothelial
progenitor cells, cell therapy approaches for lung cancer, and
bioengineering new lungs utilizing stem cells.
Workshop 6
New Gene Transfer Technologies (Joint
Session with ESGCT)
Saturday, May 21: Time: 1:15pm - 2:45pm
workshops
Pivotal to the success of genetic engineering of therapeutic
cells (e.g., immune effector cells; human stem/progenitor
cells) is the availability of adequate gene transfer technologies,
comprising both virus and non-virus based transfer methods.
To date, retro-/lentiviral gene transfer is most wide spread
in clinical applications, but bears drawback of ad random
genomic integration with related safety concerns and gene
silencing by host restriction factors. In this workshop we
present promising new developments in both non-viral and
viral gene therapy, including transposon-based methods (Dr.
Izsvák), site specific gene editing using zinc finger nucleases
(Dr. Rahman) as well as new developments in viral gene
transfer (Dr. Rethwilm). In addition prospects of translation
to clinical application will be discussed.
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Technical Applications
Track Synopses
Technical Applications
Track 1
Quality and Technical Agreements for
Cell Therapy Facilities
Thursday, May 19: Time: 7:45am - 8:45am
technical applications tracks
Do you know when you need to establish formal agreements
and with whom? Do you struggle with putting agreements
in place in your facility? Are you unsure about what content
to include that’s mutually beneficial for your material and
service providers and your organization? If you have often
asked yourself these questions then this is the session for you.
We will present approaches to developing QA and technical
agreements for facilities in the US and EU, and provide
practical guidance for drafting these documents. Having
current agreements in place protects your organization,
is good business, and is important to monitoring the
overall quality of materials and services so critical to the
manufacturing of your product.
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Technical Applications
Track 2
Safety Testing for Cell Therapy Products:
Requirements, Relevance, and New
Technologies
Thursday, May 19: Time: 3:30pm - 5:00pm
One of the many challenges of bringing any cell therapy into
the clinic and potentially toward commercialization revolves
around the issue of safety testing. Regional regulatory
guidelines can vary, making it difficult to know what level of
testing is required, as well as what kinds of test “methods”
are acceptable. As new cell therapies and associated cell
manufacturing procedures evolve, existing safety testing
needs to evolve as well. There are many different types of
“safety tests” related to manufacturing process monitoring,
as well as to the purity, identity, potency, and “sterility” of the
final product. However, current safety tests have limitations
and don’t always provide information critical to the cell
products intended use. Moreover, safety testing can be very
time consuming and costly, and thus any new technologies
which can reduce the time and cost of testing, and harmonize
the process, will be welcome in the cell therapy community.
This session will open with an overview of European and
US FDA regulatory requirements for safety testing, which
generally emphasize detection of microbial contamination,
viral adventitious agents, and tumorigenic potential.
Selection and qualification of test methods, and regulatory
expectations for product release will be covered as well.
Then, a study will be presented that demonstrates how
molecular profiling of a cell product (MSC) during culture
and expansion may reveal critical product attributes that
classical tests for safety/potency are unable to measure. This
kind of “profiling” may delineate new families of biomarkers
that are important for manufacturing effective cell therapies.
Finally, we will look to see what kinds of tools are evolving
to make safety testing and product “characterization” more
“timely”, more affordable, and more adaptable to the unique
needs associated with novel cell types, novel manufacturing
processes, and novel clinical applications.
Technical Applications
Track 3
Environmental Monitoring: How much
is enough?
Friday, May 20: Time: 7:30am - 8:30am
This session will attempt to answer this common question in
cell therapy facilities by presenting two perspectives. Lynn
O’Donnell will discuss the approach used in a non-classified
cell therapy facility in the U.S., while Philip de Vries will
present monitoring in a GMP facility in the EU. Attendees
can expect discussion of other common environmental
monitoring questions as well, such as “Do I have to validate
my EM Program?” and “How do I know how to set action
and alert levels?” Plenty of time will be allowed for audience
questions and comments.
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Technical Applications
Track 4
CD34 enumeration, how and when
2011
Friday, May 20: Time: 10:45am - 12:15pm
Friday, May 20: Time: 3:30pm - 5:00pm
In recent years, cell and gene therapies have shown the
potential to treat malignant diseases and improve degenerative
disorders of many organs including bone, muscle, nerve,
retina, skin, pancreatic islets, and blood vessels. But after
identification of an appropriate clinical target, establishment
of a novel cell or gene based therapeutic approach, and
completion of pre-clinical studies, transformation of these
research breakthroughs into new therapies for treating human
disease is often difficult. Advanced cell therapy development
such as cell transplantation, adoptive immunotherapy, gene
therapy and regenerative therapy mandate cGMP (current
good manufacturing practices) grade cell processing to
assure the safety and quality of manipulated cell products.
Therefore, one of the first steps to take from the bench to
the bedside is the design of a facility for the preparation of
clinical material for use in human clinical trials. With this come
many issues, questions and concerns relating to operating an
academic GMP facility.
There are a number of medical centers in several regions
of the world that are active in cell and gene therapy and
consequently have designed and built facilities capable of
performing cell engineering and vector production using
cGMP. In this workshop, there will be a discussion of how
differences in the expectations of research investigators
and the requirements needed for pre-clinical development
of cellular products were identified and how these were
addressed in an academic center and therefore resulted
in successful early phase cellular therapy studies. Also to
be discussed will be how sources of information within
the institution, the professional community and regulatory
agencies are developed and accessed so as to facilitate IND/
IDE submissions as well as premarket licensure/approval
submissions.
technical applications tracks
While most laboratories use the ISHAGE protocol to perform
CD34+ cell enumeration in HSC grafts, differences in reagents,
gating schemes, when and how perform viability testing as
part of their analysis and great variability still prevails. This
WS was designed to improve the quality of CD34+ cell
assessments in HSCT grafts. The topics that will be covered
include suggested improvements of the ISHAGE method and
of quality assessment of the enumeration assay. The speakers,
from both academia and industry are all well known with more
than 20 years in the field, will discuss CD34 antibodies, PMT,
compensations and gating (CD45 and CD34), different FCM
platforms, viability evaluated by 7-AAD staining and gating
of dead cells and when viability assessment is absolutely
necessary. Frank Preijers, PhD the Stem Cell Laboratory
Director/Supervisor Immunophenotyping Radboud University
Nijmegen Medical Centre, Netherlands will present quality
assurance (EQA) schemes and effective in reduction of inter
laboratory variation and improvement in assay accuracy
and viability testing. Lubomir Arseniev, MD, PhD, MBA from
Cytonet Hannover GmbH will discuss the techniques used for
CD34 enumeration in industry, quality control assays as well
as for the manufacturing procedures that are in compliance
with the Ph, Eur. and the national German regulations Joanne
Kurtzberg MD, PhD Professor of Pediatrics, Professor of
Pathology, Director, Pediatric Blood and Marrow Transplant
Program and Director, Carolinas Cord Blood Bank, Duke
University Medical Center, Durham, North Carolina, USA
will present a clinical approach of enumeration on fresh and
thawed cord blood cells and share their experience with both
CD34 and ALDH staining.
Technical Applications
Track 5
Establishing GMP Facilities with QA
Oversight in Academic Centers for
Phase I/II Clinical Trials
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Technical Applications
Track 6:
The Essentials of Validation,
Qualification and Verification
Saturday, May 21: Time: 7:30am - 8:30am
technical applications tracks
Who’s the man behind the curtain? Are you caught up in
semantics and the confusion associated with when to
validate vs when to verify? Come learn and be prepared to
participate in this dynamic interactive workshop. All new
equipment, processes, and products that are critical to the
safety, purity, or potency of products need to be qualified
and validated before use. Speakers will share examples of
well formatted validation plans with the participants and
discuss how to prepare and operate with the corresponding
SOPs. Participants will review specific examples of equipment
and process validations (i.e. cryopreservation and thawing;
cell processing and flowcytometric quality control). Upon
completion of this workshop, attendees will take away
tangible verification and validation examples as well as
resources that can be used when you get back to the office
on Monday.
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Technical Applications
Track 7
ISBT 128 Labeling: We’ve implemented,
and so can you!
Saturday, May 21: Time: 10:45am - 11:45am
ISBT 128 is a coding and labeling system, which was originally
developed for blood and blood products to improve quality,
safety and traceability in blood banking by ISBT. Today the
standard is managed by ICCBBA. Since 2005, the Cellular
Therapy Coding and Labeling Advisory Group (CTCLAG)
supported by most of the worldwide operating organisations
in the field of cellular therapy (including, ISCT, JACIE/FACT)
has been working on the ISBT 128 coding and labeling of
CT-products. In this session, a short overview of the current
activities of the CTCLAG will be given. Furthermore, two
user’s will share their experience: Boris Calmels from France
and Giovanni Cameron from Canada both will give technical
information on their implementation project in different
settings. In this session, you will also have the opportunity
to ask technical questions, share your concern, suggest
improvements and interact with other participants on
detailed technical CT-related issues.
Technical Applications
Track 8
Process Development: Optimization
and qualification of processes for
maintaining quality parameters of
therapeutic cells
Saturday, May 21: Time: 1:15pm - 2:45pm
Process Development is a unique discipline that is not taught
in University and is typically learned on the job. Because of
this, references to best practices in Process Development
are difficult to find in manuscripts or books. This session will
cover the development processes that span the range of
manufacturing processes, including 1) Cell Culture processes
and harvest (upstream processing), 2) volume reduction
and washing of harvested cells prior to final product
formulation, and 3) formulation, final container choice,
filling and cryopreservation of final product. A focus on the
critical quality parameters of therapeutic cells that must be
maintained at each stage will be addressed.
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
Strategies for Commercialization
Track Synopses
Strategies for
Commercialization Track 1
Positioning for Phase III Manufacturing
potency testing, and strategies for effective qualification
studies to bridge changes in assay methods.
Thursday, May 19: Time: 7:45am - 8:45am
Strategies for
Commercialization Track 3
Advanced Automation for Autologous
Processing
CMC needs to be “locked-in” for a pivotal clinical trial
(typically Phase 3), which takes place when the clinical
safety and proof of concept has been established. There is
a window of opportunity before the start of the pivotal trial
to make decisions and investments to ensure manufacture
of a product of consistent quality and commercial success.
This session will focus on the activities, decisions, and
investments to align the need for compliance with regulatory
requirements and commercialization of a cell based product
before the start of a pivotal clinical trial.
Thursday, May 19: Time: 11:00am - 12:15pm
Effective characterization testing is the cornerstone of
successful cell therapy product and process development.
A basic understanding of key characteristics is essential from
the outset. This characterization foundation - of the product,
cellular raw material, and process intermediates - grows more
detailed and extensive in the course of preclinical and clinical
development. Characterization testing is commonly thought
of in terms of safety, purity, identity, potency, and stability.
Of these, potency testing, measurement of the product’s
relevant biological function, presents particularly formidable
challenges, from selecting and controlling assays, to
establishing specifications, and to qualification and validation.
The product’s biological function may involve interactions
with device components, local cell populations, and other
microenvironment effects. In vitro measurement of product
function may require multiple functional and non-functional
assays, and unique reference standards. Multiple candidate
potency assays may be evaluated, necessitating qualification
studies to bridge changes in test methods. This session will
review common questions in potency testing development and
qualification, current European and US regulatory guidance
and expectations, guidelines for controlling and validating
As Autologous and Patient-specific products continue
through clinical development, it is important to prepare for
commercialization of these unique therapies. Once these
therapies are on the market, tens of thousands of patient
product doses will be required to be manufactured for
a variety of products. At this level of processing, greater
than 100 patient samples must be received every day, and
the same number of final products must be processed,
tested, and released daily. This level of manufacturing will
require extensive automation at almost every step, including
processing, analytical testing, and product release. This
session will outline different approaches to automation,
some technologies available today, and importantly when
to begin planning for, and implementing automation during
clinical development.
Strategies for
Commercialization Track 4
Risk Assessments
Friday, May 20: Time: 7:30am - 8:30am
The concept of manufacturing quality risk management
(QRM) has been endorsed by regulatory authorities in the ICH
regions and beyond for some time in the form of ICH Q9. ICH
Q9 was not written with cell-based products in mind, but this
session will explore how this might be approached and discuss
the outcomes of one such attempt. Taking the concept of
risk management further, the EMA’s guideline on cell-based
medicinal products and a recent revision of the requirements
for marketing authorisation for ATMP’s introduced the concept
of a risk-based approach. Although only at the concept paper
stage, the risk-based approach appears to go further than
manufacturing QRM and offer the opportunity to focus the
Strategies for commercialization
Strategies for
Commercialization Track 2
Cell Characterization, Potency, and
Comparability Studies
Thursday, May 19th: Time: 3:30pm - 5:00pm
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whole of product development based on risk. The session will
discuss whether the risk-based approach offers a short-cut for
ATMP development or is this merely an acknowledgment of
the difficulties in developing them?
Strategies for
Commercialization Track 5
Decreasing Corporate Risk for Cell
Therapy Programs
Friday, May 20: Time: 10:45am - 12:15pm
Strategies for commercialization
This session will focus on key strategies companies can
employ in order to decrease the risk associated with investing
in cell therapy commercialization programs. Strategies to
decrease time to market, increase odds of clinical success,
improve globalization and Regulatory compliance, and to
allocate risk across programs will be explored.
30
Dr Natalie Mount will discuss Pfizer’s approach to smart
clinical trial design, David James of Invetech will present
an argument on why, when and how to invest in process
automation, and Paul Anderson of OrthoCell will discuss
portfolio diversification for regenerative medicine companies.
Dr Dawn Driscoll will Chair, and will briefly discuss the FDA’s
SPA program, as part of a corporate risk reduction strategy.
Strategies for
Commercialization Track 6
Challenges of commercial development
of pluripotent hES
Friday, May 20: Time: 3:30pm - 5:00pm
This session will focus on the bottlenecks and difficulties
which can be anticipated to challenge the commercialization
of hES-derived therapies. First, quantitative modeling will be
used to translate anticipated patient populations, dosages
and market penetrance into predicting the demands which
will be placed on cell therapy manufacturing unit operations.
Secondly, these will be mapped onto the equivalent challenges
which have faced classical biologics, with consideration of
how this field overcame the difficulties. Thirdly, a similar
approach will be taken to analyze the regulatory path taken
by biologics and areas of commonality and difference with
cell therapies..
Strategies for
Commercialization Track 7
Personalized approach to cell and gene therapy
Saturday, May 21: Time: 7:30am - 8:30am
This session will present and discuss cell and gene therapies
that have reached the stage of Phase 2 clinical trial.
Dr. Ronnda Bartel of Aastrom Biosciences will present
“Ixmyelocel-T - A New Therapy for Severe Chronic
Cardiovascular Disease”. Ixmyelocel-T is a disease
modifying therapy with multi-functional properties including
tissue remodeling, immuno-modulation and the promotion
of angiogenesis, which is targeted to address the multiple
underlying causes of many severe, chronic cardiovascular
diseases such as CLI. This patient specific cell therapy is
manufactured from the patient’s own bone marrow using
Aastrom’s proprietary, automated closed manufacturing
system. Ixmyelocel-T is composed of a mixture of cell
types normally found in bone marrow as well as expanded
mesenchymal stromal cells and alternatively activated
macrophages. This presentation will give an overview
of the ixmyelocel-T product manufacture, preclinical
characterization and interim results of the Phase 2 clinical
study in critical limb ischemia.
Dr. Philippe Leboulch of the Unversity of Paris (CEA-INSERM)
and Harvard Medical School will present “Lentiviral
therapies for genetic disorders: illustration with
adrenoleukodystrophy and the β-hemoglobinopathies”,
the two first approved human trials worldwide that make
use of lentiviral vectors for the treatment of genetic diseases.
After years of optimization, gene therapy has seen clear
evidence of clinical benefit in selected patients, and bluebird
bio of Cambridge, MA, is developing these approaches
towards commercialization. The β-hemoglobinopathies
(β-thalassemia and sickle cell disease) are the most prevalent
inherited disorders worldwide. Gene therapy of these
diseases is especially challenging given the requirement for
massive hemoglobin production and the lack of selective
advantage for corrected hematopoietic progenitors. Our
trial shows that, 4 years after lentiviral β-globin ex vivo
gene transfer to hematopoietic stem (HSC) cells, an adult
patient with severe βE/β0-thalassemia dependent on monthly
transfusions since early childhood has become transfusion
independent for the past 3 years. Potential safety issues will
also be discussed. X-linked adrenoleukodystrophy (ALD) is a
severe brain demyelinating disease in boys that is caused by
a deficiency in ALD protein. Four children with the disease
May 18–21, 2011
De Doelen Congress Centre
Rotterdam, The Netherlands
were submitted to lentiviral gene therapy. Up to 4 years
later, disease progression slowed down or even halted, a
clinical outcome comparable to that achieved by allogeneic
transplantation.
Strategies for
Commercialization Track 8
Strategies for Allogeneic Cell Therapy
Commercialization
Saturday, May 21: Time: 1:15pm - 2:45pm
Mesenchymal cell therapies: from concept
to clinic
Strategies for commercialization
A number of groups that develop allogeneic mesenchymal
cell-based therapies have made considerable advances
towards the commercialization of their products. This
session will describe and discuss the potential benefits of
different tissue sources such as bone marrow and placenta,
and their different cell populations, for the successful
commercial development of off the shelf cell therapies. Key
commercial considerations include raw material availability,
intrinsic mechanistic capacity, ease and cost effectiveness of
production, utility, distribution logistics and reimbursement.
31
Meeting Room Directory
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• Conference Office
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32
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