Lecture 38
Plantibodies
ANTIBODIES PRODUCED FROM PLANTS
• Functional antibodies can be produced from plants
• Targeted to intercellular space, chloroplast, seeds
and tubers
• Benefit for topical immunotherapy
• Can be produced from plants in large quantities
Contd...
• Plantibodies provides increased stability
e.g: Secretory Ig A
• Plants can assemble complex secretory antibodies
e.g: Construction of tobacco plants
expressing 4 transgenes
• Quadruple transgenics efficiently assembled
secretory immunoglobulins
(Smith & Glick, 2000)
Anti-rabies virus mAb
After exposure treated with Ab
Used to be made in horses
First mAb made in transgenic plants
4 genes – 2 H, 2 L
Transgenic plant for each one and
crossing plants
Later used single binary vector with two
promoters
Full-size monoclonal antibodies recently produced
in transgenic plants
Abs expressed in transgenic
plants
Constant
domains
Variable Light chain
Variable Heavy chain
Recombinant hinge region
Functional Abs
Need to be properly folded and assembled
Need disulfide bond formation and
glycosylation
Down stream processing:
Purification of Ab mostly with Protein A
or G
Glycosylation is different in plants
β 1,2 Xylose and α 1,3 fucose
Retain in ER, only mannose is attached
–Shorter half-life of Ab
Glycosylation of Ab
Full-size Ab
Large single-chain Ab
Camelid heavy-chain Ab
Minibodies and Fab fragments don’t get glycosylated
Glycosylation in Golgi
Antibodies: a compelling success story

high specificity: in vitro and in vivo diagnostics

low toxicity: therapeutic applications

high drug approval rates (24 approved mAbs)

major products in biotechnology (~240 in clinical
trials)

inherently stable human proteins

injectable, topical and oral applications

applicable for chronic conditions

potential long-lasting benefits
Production Costs for Antibodies
Production costs
cost in $ /gram
hybridomas
1000
transgenic animals
transgenic plants
100
10
Source: Daniell et al. (2001) TIPS 6, 219-226
E. coli & yeast
Tr. animals and
animal cells
Transgenic
plants
Comparison of Mammalian and Plant-produced
Antibodies

peptide sequence: identical

correct cleavage of Ig-derived signal peptides

kinetics & affinity: identical

stability in seeds > 30 months

antibody types: plant system more versatile (sIgA)

post-translational processing: different

core glycan identical, terminal sugar different plus xylose & fucose

antigenicity & clearance: apparently identical (shorter half-life)