平成 27 年 12 月 24 日 各 位 オンコセラピー・サイエンス株式会社 代表取締役社長 森 正治 （コード番号４５６４ 東証マザーズ） （問い合せ先）取締役管理本部長 山本 和男 電話番号 ０４４－８２０－８２５１ ＜マザーズ＞投資に関する説明会開催状況について 以下の通り、投資に関する説明会を開催いたしましたので、お知らせいたします。 記 開催状況 開催日時 平成 27 年 12 月 1 日（火） 15：00～16：00 開催方法 対面による実開催 開催場所 TKP東京駅丸の内会議室 東京都千代田区丸の内3-1-1 帝劇ビルB1 説明会資料名 オンコセラピー・サイエンス株式会社 会社説明会資料 添付資料 投資説明会において使用した資料 以上 䜸䞁䝁䝉䝷䝢䞊䞉䝃䜲䜶䞁䝇ᰴᘧ♫㻌 ♫ㄝ᫂㻌 ௦⾲ྲྀ⥾ᙺ♫㛗㻌 ᳃㻌 ṇ ᖹᡂ27ᖺ12᭶1᪥ 1 䜸䞁䝁䝉䝷䝢䞊䞉䝃䜲䜶䞁䝇䠄OTS)䛜┠ᣦ䛩䜒䛾 2 ┠ḟ 䠍䠅ᢠ䛜䜣䝬䞊䜿䝑䝖䛾ᴫἣ 䠎䠅OTS䛾≉㛗䛸⤒Ⴀ᪉㔪 䠏䠅◊✲㛤Ⓨ䝟䜲䝥䝷䜲䞁䛸ᙜᮇ䛾άື 䠐䠅◊✲㛤Ⓨ䛾㐍ᤖ≧ἣ 㻌 పศᏊ◊✲㛤Ⓨ≧ἣ 㻌 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠑䠅㈨ᩱ㞟 3 ᡂ㛗䛩䜛ᢠ䛜䜣䜾䝻䞊䝞䝹䝬䞊䜿䝑䝖 ศᏊᶆⓗ⸆䜢୰ᚰ䛸䛧䛯᪂つ㛤Ⓨရ䛾ୖᕷ䛻䜘䜚䚸㐣ཤ10ᖺ䛷ᢠ 䛜䜣䛿3ಸ㏆䛟䜎䛷䝬䞊䜿䝑䝖䝃䜲䝈䛜ᣑ䛧䛶䛔䜛䚹 ᢠ䛜䜣䛾ୖ᥎⛣䠄䜾䝻䞊䝞䝹䠅 Mil USD 90,000 3൨䝗䝹ᮍ‶ CAGR㻌 11% 80,000 70,000 3䡚10൨䝗䝹 䠄32ရ┠䠅 60,000 50,000 10൨䝗䝹௨ୖ 䠄23ရ┠䠅 40,000 30,000 20,000 10,000 0 2005 Source:㻌 Uto Brain 2015 2006 2007 2008 2009 2010 2011 2012 2013 2014 4 䜰䞁䝯䝑䝖䝯䝕䜱䜹䝹䝙䞊䝈䛾ᙉ䛔䛜䜣㡿ᇦ 䛜䜣䛸䛔䛖Ẽ䛾ከᵝᛶ䚸」㞧䛺䝯䜹䝙䝈䝮䛻䜘䜚䚸⒪ຠᯝ䛜㧗 䛔᪂つ䛾ศᏊᶆⓗ⸆䛻ᑐ䛩䜛ᙉ䛔䜰䞁䝯䝑䝖䝙䞊䝈䛜Ꮡᅾ䛩䜛 ᭷ຠ䛺 ศᏊ ᶆⓗ⸆ 䛺䛧 䜾䝻䞊䝞䝹 ᡭ〇⸆ ᴗ14♫ 䛾 㛤Ⓨ 䝟䜲䝥 䝷䜲䞁ᩘ 㐺ᛂ䛾䛒䜛ศᏊᶆⓗ⸆䛜 䜎䛰Ꮡᅾ䛧䛺䛔 㐺ᛂ䛾䛒䜛ศᏊᶆⓗ⸆ 䜢ᢞ䛧䛶䜒ዌຌ䛧䛺䛔 ᭷ຠ䛺 ศᏊ ᶆⓗ⸆ 䛒䜚 䠄㐺ᛂᩘ 䝧䞊䝇䠅 ዌຠ⋡ 10䡚30䠂* 䠆䛜䜣䛾Ⓨᶵᗎ䛻䜘䛳䛶䛿ዌຠ⋡䛾㠀ᖖ䛻㧗䛔ᢠ䛜䜣䜒Ꮡᅾ䛩䜛䛜䚸䛾ᝈ䛸ẚ䜉䜛䛸䚸య䛸䛧䛶䛿ᢠ䛜䜣䛾ዌຠ⋡䛿ప䛔 5 Source:㻌 ᪥⤒䝞䜲䜸䝔䜽䝜䝻䝆䞊䚸ᙜ♫ศᯒ ὀ┠䛾㧗䜎䜛䛜䜣䛾ච⒪ἲ ච䝏䜵䝑䜽䝫䜲䞁䝖㜼ᐖ䛾Ⓩሙ䛸䚸NGS*䜢ά⏝䛧䛯චᛂ⟅䛾 ゎᯒᢏ⾡䛾㐍Ṍ䛻䜘䜚䚸䛜䜣䛾චศ㔝䜈䛾㛵ᚰ䛜㧗䜎䛳䛶䛔䜛 䝍䞊䝀䝑䝖 䛜䜣⣽⬊ ᫂☜䠄䝢䞁䝫䜲䞁䝖䠅 యⓗ zศᏊᶆⓗ⸆ z⣽⬊ẘ⣔䛾⸆ 㻌 - పศᏊ 㻌 - ᢠయ 䠄ᗣ䛺⣽⬊䜒ྵ䜑䛶ศ 䜢㜼ᐖ䠅 ච 䜰䜽䝉䝹 z䛜䜣䝽䜽䝏䞁 ᶵᵓ 䛾ஹ㐍 㻌 - 䛜䜣ᢠཎ䠄䝨䝥䝏䝗䝽䜽䝏䞁䠅 z㠀≉␗ⓗච⒪ἲ 㻌 - 䛜䜣≉␗ኚ␗ᢠཎ䠄䝛䜸䜰䞁䝏䝀䞁䝽䜽䝏䞁䠅 䝤䝺䞊䜻 zච䝏䜵䝑䜽䝫䜲䞁䝖㜼ᐖ 䛾ᢚไ 㻌 䠄䝯䝷䝜䞊䝬䛾䜘䛖䛺ኚ␗䛾ከ䛔䛜䜣䛻 㻌 㻌 ᑐ䛩䜛᭷ຠᛶ䛜㧗䛔䠅 ᵬᵥᵱửဇẲẺᴾ ầỮἄἠἲỉᚐௌầӧᏡỆᴾ ίᵧᶋᶋᶓᶌᶍᶎᶆᵿᶐᶋᵿᶁᶍᶅᶃᶌᶍᶋᶇᶁᶑὸᴾ 䠆NGS䠖 Next Generation Sequencer 䠄ḟୡ௦䝅䞊䜿䞁䝃䞊䠅 6 ┠ḟ 䠍䠅ᢠ䛜䜣䝬䞊䜿䝑䝖䛾ᴫἣ 䠎䠅OTS䛾≉㛗䛸⤒Ⴀ᪉㔪 䠏䠅◊✲㛤Ⓨ䝟䜲䝥䝷䜲䞁䛸ᙜᮇ䛾άື 䠐䠅◊✲㛤Ⓨ䛾㐍ᤖ≧ἣ 㻌 పศᏊ◊✲㛤Ⓨ≧ἣ 㻌 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠑䠅㈨ᩱ㞟 7 㻻㼀㻿䛾㠉᪂ⓗᇶ┙ᢏ⾡㻌 䊻㻌 ⸆䝰䝕䝹㻌 㻝㻚㻌᪂㩭䛷ከᩘ䛾⮫ᗋ᳨య䠄䝃䞁䝥䝹䠅㻌 㻙 ⣙䠍䠌䠌䠌௨ୖ䛾⮫ᗋ᳨య䠄ᝈ⪅ᩘ 㻞㻜䡚㻤㻜 ྡ㻛 䛜䜣✀㻕 㻞㻚㻌䛜䜣≉␗ⓗ㑇ఏᏊ䛾≉ᐃ㻌 㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻙㻌㻸㼍㼟㼑㼞㻌㻹㼕㼏㼞㼛㼎㼑㼍㼙㻌㻹㼕㼏㼞㼛㼐㼕㼟㼟㼑㼏㼠㼕㼛㼚㻌㻔㻸㻹㻹㻕㻌㼟㼥㼟㼠㼑㼙㻌 㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 䛜䜣⣽⬊䛚䜘䜃ṇᖖ⣽⬊䛾㑇ఏᏊⓎ⌧䡿䢚䡬䡼䢉䢚䡬䡹ᵓ⠏㻌 㻌㻌㻌㻌㻌㻌㻙㻌⊂⮬䛾㻌㼏㻰㻺㻭㻌䝬䜲䜽䝻䜰䝺䜲ゎᯒ㻌 㻌 㻟㻚㻌䛜䜣⣽⬊䛾⏕Ꮡ䜎䛯䛿ቑṪ䛻ᚲ㡲䛷䛒䜛䛛䛾☜ㄆ㻌 㻌 㻙㻌㻾㻺㻭ᖸ΅ἲ䛻䜘䜛㜼ᐖ䛾☜ㄆ㻌 㻠㻚㻌㻟㻝䛾䝠䝖ṇᖖ⮚ჾ⣽⬊䛻䛚䛡䜛Ⓨ⌧䛾☜ㄆ㻌 㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻙㻌㔜せ䛺䝠䝖ṇᖖ⮚ჾ⣽⬊䛷Ⓨ⌧䛧䛶䛔䛺䛔㻌 8 䛜䜣⣽⬊䞉ṇᖖ⣽⬊䛾㑇ఏᏊ䜢㼏㻰㻺㻭㻌䝬䜲䜽䝻䜰䝺䜲㻌ゎᯒ㻌 㼏㻰㻺㻭㻌䝬䜲䜽䝻䜰䝺䜲㻌 RNA amplification ⭘⒆㻌 䛜䜣⣽⬊㻌 aRNA RNA Laser Microbeam Microdissection (LMM) ṇᖖ⤌⧊ 䠄Ⓨ⏕ẕᆅ䠅㻌 RNA ṇᖖ⣽⬊㻌 aRNA RNA amplification 㻟㻞㻘㻜㻜㻜㻌㑇ఏᏊ㻌 9 ೃ⿵㑇ఏᏊ䛾㑅ᢥ Uterus Placenta Testis Ovary Thymus Thyroid Salivary Grand Fetal Lung Mammary Grand Prostate Fetal Liver Fetal Brain Fetal Kidney Trachea Skeletal Muscle Brain Spinal Cord Spleen Lymph Node Colon Pancreas Small Intestine Heart Stomach Liver Lung LMMID Bone Marrow CRC219 CRC201 CRC199 CRC154 CRC197 CRC129 CRC124 CRC128 CRC123 CRC86 CRC85 Kidney ṇᖖ⤌⧊䛻䛚䛡䜛Ⓨ⌧䝥䝻䝣䜯䜲䝹㻌 䛜䜣䛻䛚䛡䜛Ⓨ⌧䝥䝻䝣䜯䜲䝹㻌 A0908 A1605 A0212 厮 台 又 㧗 Ⓨ ⌧ A2241 A2092 A4123 A5287 A0415 B0158 A7147 B7734 A2510 A4236 ೃ ⿵ 㑇 ఏ Ꮚ 㻌 㻌 去 召 㑇 ఏ Ꮚ A5109 A1065 B4036 B0338 C3838 C7939 A0251 A1904 A2233 A2243 A8220 A8196 A2239 ⭘⒆⤌⧊䛚䜘䜃ṇᖖ⤌⧊୧᪉䛾Ⓨ⌧䝥䝻䝣䜯䜲䝹䛻ᇶ䛵䛟ೃ⿵㑇ఏᏊ䛾㑅ᢥ 10 10 㠉᪂ⓗᇶ┙ᢏ⾡䛻ᇶ䛵䛟⸆䝰䝕䝹䛸◊✲㛤Ⓨ పศᏊ་⸆ 㑇ఏᏊ㛵㐃 ሗ ⸆᪂つᶆⓗ≉ᐃ 䛜䜣⣽⬊䛻Ⓨ⌧䛧ṇᖖ⣽⬊䛻Ⓨ ⌧䛧䛺䛔⥙⨶ⓗ㑇ఏᏊゎᯒ 䝕䞊䝍䝧䞊䝇 㑇ఏᏊ㛵㐃 ሗ 㑇ఏᏊ㛵㐃 㐃 㑇ఏᏊ㛵㐃 ሗ ሗ 㑇ఏᏊ㛵㐃 ሗ OTS167 OTS964➼ ⡿ᅜ䛷➨Ϩ┦⮫ᗋヨ㦂 ⮫ᗋヨ㦂๓䛾㠀⮫ᗋヨ㦂ᐇ 䛜䜣䝽䜽䝏䞁 OTSGC-A24➼ 㻌 㻌 ᪥ᮏ䚸䜰䝆䜰䛷⮫ᗋヨ㦂 䝨䝥䝏䝗䝽䜽䝏䞁ᑟฟ῭ ᢠయ་⸆ OTSA101 䝣䝷䞁䝇䛷➨Ϩ┦⮫ᗋヨ㦂 11 㻻㼀㻿䛾◊✲㛤Ⓨᡓ␎㻌 • •䠫䠰䠯㠉᪂ⓗᢏ⾡ᇶ┙䛻ᇶ䛵䛟⸆䝰䝕䝹䛛䜙㻌 㻌 ᪂⸆ೃ⿵䜢⥅⥆ⓗ䛻〇䛩䜛㻌 䋻㻌 䝀䝜䝮⸆㻌 㻌㻌㻌 㻌 •ప •పศᏊ་⸆䛿䝅䜹䝂Ꮫ䜢ึ䜑䛸䛩䜛⡿ᅜ䛾ඃ䜜䛯Ꮫ䞉㻌㻌 㻌 ◊✲ᶵ㛵䛾ᑓ㛛་䛸䛾༠ຊ䜢㔜ど䛧䚸䜾䝻䞊䝞䝹䛺どⅬ䛷㻌 㻌 ⮫ᗋヨ㦂䜢㎿㏿䛻㐙⾜䛧䚸Ⰻ㉁䛾⮫ᗋ䝕䞊䝍䜢ྲྀᚓ䛩䜛㻌 㻌 •䛜䜣䝽䜽䝏䞁㡿ᇦ䛷䛿䚸䛜䜣≉␗ⓗ䝨䝥䝏䝗䝽䜽䝏䞁䛚䜘䜃㻌 •䛜 㻌 㼀㻯㻾㓄ิゎᯒᴗ䜢᥎㐍䛧䛶䚸䛜䜣ච⒪ἲ䛻㈉⊩㻌 㻌 •ᢠ •ᢠయ་⸆䛿䚸䝣䝷䞁䝇䛷ᐇ୰䛾㻻㼀㻿㻭㻝㻜㻝䛾㻌 㻌 ➨䊠┦⮫ᗋヨ㦂䜢╔ᐇ䛻⤊䛧䚸ḟ┦䜢┠ᣦ䛩㻌 㻌 㻌 12 ⤒Ⴀ᪉㔪䠄యീ䠅 Ἁỽἆٻᴾ 㻻㼀㻿 ίσӷᄂᆮὸᴾ 㠉᪂ⓗ㻌 ⓗ ᇶ┙㻌 ᢏ⾡㻌 ⾡ 䛜䜣䝽䜽䝏䞁 䊼㻌 䛜䜣⣽⬊䛻Ⓨ⌧䛧 ṇᖖ⣽⬊䛻Ⓨ⌧䛧䛺䛔 ⥙⨶ⓗ㑇ఏᏊゎᯒ 䝕䞊䝍䝧䞊䝇䠆 䝀䝜䝮 ⸆㻌 పศᏊ་⸆ ᢠయ་⸆ ⸆᪂つ 䝍䞊䝀䝑䝖≉ᐃ ᴾ ࢘ᅈᴾ ᴾ ᴾ ੩ઃέᴾ ᴾ ᴾ ᙌᕤ˖ಅᴾ ࢘ᅈᴾ 䠆ᖹᡂ13ᖺ䛛䜙25ᖺ䛻䛛䛡䛶ᐇ䛧䛯ᮾிᏛ་⛉Ꮫ◊✲ᡤ䛸䛾ඹྠ◊✲䛾ᡂᯝ䛻ᇶ䛵䛟 13 ⤒Ⴀ᪉㔪䠄䜎䛸䜑䠅 䠍㻚㻌㻌ᇶ♏ 䠍㻚 ♏◊✲䛾⥅⥆ⓗ䛺ᐇ㻌 9 ᙜ♫⊂⮬䠇䝅䜹䝂䛸䛾ඹྠ◊✲➼㻌 㻌 䠎㻚㻌㻌 䠎 㻚 ⸆◊✲䛾╔ᐇ䛺᥎㐍㻌 䋻㻌 䝀䝜䝮⸆㻌 9 పศᏊ་⸆䚸䛜䜣≉␗ⓗ䝨䝥䝏䝗䝽䜽䝏䞁䚸ᢠయ་⸆㻌 㻌 䠏㻚㻌㻌 䠏 㻚 ⮫ᗋ㛤Ⓨ䛾☜ᐇ䛛䛴㎿㏿䛺᥎㐍㻌 9 ᙜ♫⊂⮬䠇ᥦᦠඛ〇⸆ᴗ㻌 9 㠀⮫ᗋヨ㦂䝕䞊䝍䛻ᇶ䛵䛟㐺ᛂᣑ㻌 㻌 䠐㻚㻌㻌 䠐 㻚 ᪂つᥦᦠඛ䛾㛤ᣅ䛚䜘䜃᪤Ꮡᥦᦠඛ䛸䛾㻌 㻌 㻌 㻌ᥦᦠᴗ䛾☜ᐇ䛺᥎㐍㻌 㻌 㻌 9 ᡓ␎ⓗᑐヰ䠇ഃ㠃ᨭ䞉ᚋ᪉ᨭ㻌 9 T⣽⬊䞉B⣽⬊ཷᐜయゎᯒ䛾ᴗ䚸⏬ᮇⓗ䛺ච⒪ ἲ䛾㛤Ⓨ 14 ┠ḟ 䠍䠅ᢠ䛜䜣䝬䞊䜿䝑䝖䛾ᴫἣ 䠎䠅OTS䛾≉㛗䛸⤒Ⴀ᪉㔪 䠏䠅◊✲㛤Ⓨ䝟䜲䝥䝷䜲䞁䛸ᙜᮇ䛾άື 䠐䠅◊✲㛤Ⓨ䛾㐍ᤖ≧ἣ 㻌 పศᏊ◊✲㛤Ⓨ≧ἣ 㻌 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠑䠅㈨ᩱ㞟 15 ◊✲㛤Ⓨ䝟䜲䝥䝷䜲䞁䠄2015.12⌧ᅾ䠅 㣗㐨䛜䜣䛾➨Ϫ┦ヨ㦂䠄ሷ㔝⩏ᑟฟ῭䠅䜢➹㢌䛻䚸3ศ㔝䠄పศᏊ䚸 䝨䝥䝏䝗䝽䜽䝏䞁䚸ᢠయ䠅䛾䛩䜉䛶䛷䚸㦂ẁ㝵䛾㛤Ⓨ䛜㐍䜣䛷䛔䜛 ప ศ Ꮚ 吱 吮 吘 吠 呆 吆 吘 呉 ྜ≀ ᶆⓗ/ᝈ OTS167 MELK OTS964➼ TOPK 㻙㻌 㻡✀㢮䛾ᶆⓗ䜢 ྠᐃ῭䜏㻌 㻿㻙㻡㻤㻤㻠㻝㻜㻌 䠄ሷ㔝⩏䜈䠅㻌 ᑟฟ῭䜏䚸㛤Ⓨᨭ㻌 㣗㐨䛜䜣㻌 䠄ሷ㔝⩏䜈䠅 ᑟฟ῭䜏䠅 ⭤⬔䛜䜣㻌 㢌㢕㒊䛜䜣㻌 䠄ᑠ㔝䜈䠅 ᑟฟ῭䜏 ⫢⣽⬊䛜䜣㻌 䠄ሯ䜈䠅 ᑟฟ῭䜏 ⭠䛜䜣㻌 OTSA101 ⭷⫗⭘ ᢠ య 䠄༠Ⓨ㓝䜻䝸䞁䜈䠅 ᑟฟ῭䜏 ᇶ♏◊✲ 㛤Ⓨྜ≀ 㠀⮫ᗋヨ㦂 ➨Ϩ┦ ⮫ᗋヨ㦂 ➨ϩ┦ ⮫ᗋヨ㦂 ➨Ϫ┦ ⮫ᗋヨ㦂 䜰䝹䝒䝝䜲䝬䞊 ὀ䠖ᐇ⥺䛿ᙜ♫㛤Ⓨ୰䠄㛤Ⓨᨭྵ䜐䠅䚸Ⅼ⥺䛿ᑟฟ῭䜏䠄ᑟฟඛ䛾〇⸆♫䛜㛤Ⓨ୰䠅 16 ᙜᮇ䛾άື䝃䝬䝸䞊䠄2015.6䡚11䠅 z ศᏊᶆⓗపศᏊྜ≀ ¾ MELK 9 OTS167䛿䝅䜹䝂䛷➨Ϩ┦⮫ᗋヨ㦂䜢㟼⬦ෆᢞ䛻䜘䜚ᐇ୰䚹㏣ຍ 䛷⤒ཱྀᢞ䛻䜘䜛ヨ㦂䛾ᐇ䜢Ỵᐃ䠄6᭶䠅 ¾ TOPK 9 䝅䜹䝂Ꮫ䜾䝹䞊䝥䜘䜚䚸ணᚋ䛾ᝏ䛔FLT3-ITDኚ␗䜢ᣢ䛴ᛴᛶ㦵㧊ᛶⓑ ⾑䝬䜴䝇䝰䝕䝹䛷䛾᭷ຠᛶ䜢♧䛩ㄽᩥⓎ⾲䠄10᭶䠅 9 ⡿ᅜ❧䛜䜣◊✲ᡤ䛜ᥦ౪䛩䜛ྜ≀ホ౯䝥䝻䜾䝷䝮䛻᥇ᢥ䠄11᭶䠅 ¾ SUV39H2 9 䝅䜹䝂Ꮫ䜾䝹䞊䝥䜘䜚䚸ᛴᛶ䝸䞁䝟ⱆ⌫ᛶⓑ⾑䛷䛾᭷ຠᛶ䜢♧၀䛩 䜛ㄽᩥⓎ⾲䠄10᭶䠅 z 䛜䜣䝨䝥䝏䝗䝽䜽䝏䞁 ¾ ሷ㔝⩏䛻ᑟฟ῭䜏䛾S-588410䠄5✀㢮䛾䝨䝥䝏䝗䝽䜽䝏䞁䜢ΰྜ䠅 9 ⭤⬔䛜䜣䛻ᑐ䛩䜛 ᪥Ḣ➨ϩ┦⮫ᗋヨ㦂䛻䛴䛔䛶䚸┠ᶆᩘ䛾Ⓩ㘓 䛜䠄9᭶䠅 z ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 ¾ TCRゎᯒ䝃䞊䝡䝇 9 ♫ෆ䛷䛾䛜䜣䝽䜽䝏䞁ᴗ㛤Ⓨ䛻ຍ䛘䛶䚸〇⸆ᴗ䚸་⒪ᶵ㛵䚸◊✲ᶵ 㛵➼䛻ᑐ䛩䜛ཷク䝃䞊䝡䝇㛤ጞ䠄9᭶䠅 17 ┠ḟ 䠍䠅ᢠ䛜䜣䝬䞊䜿䝑䝖䛾ᴫἣ 䠎䠅OTS䛾≉㛗䛸⤒Ⴀ᪉㔪 䠏䠅◊✲㛤Ⓨ䝟䜲䝥䝷䜲䞁䛸ᙜᮇ䛾άື 䠐䠅◊✲㛤Ⓨ䛾㐍ᤖ≧ἣ 㻌 పศᏊ◊✲㛤Ⓨ≧ἣ 㻌 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠑䠅㈨ᩱ㞟 18 పศᏊ◊✲㛤Ⓨ≧ἣ 䠍䠅MELK㜼ᐖ 㻌 㻌 㻻㼀㻿㻝㻢㻣䠄㻹㻱㻸㻷㜼ᐖ䠅㛤Ⓨ≧ἣ㻌 㻌 㻌 ศᏊᶆⓗ㻹㻱㻸㻷䛾≉㛗㻌 㻌 㻌 㻻㼀㻿㻝㻢㻣䠄㻹㻱㻸㻷㜼ᐖ䠅䛾≉㛗 䠎䠅TOPK㜼ᐖ䠄㠀⮫ᗋヨ㦂୰䠅㻌 㻌 㻌 ศᏊᶆⓗ㼀㻻㻼㻷䛾≉㛗㻌 㻌 㻌 㼀㻻㻼㻷㜼ᐖ䠄㻻㼀㻿㻥㻢㻠➼䠅䛾≉㛗㻌 19 OTS167(MELK㜼 㜼ᐖ䠅㛤Ⓨ≧ἣ z ➨Ϩ┦⮫ᗋヨ㦂䜢ᐇ୰䠄䝅䜹䝂Ꮫ䠅 ¾ 㐺ᛂ䠖ᶆ‽⒪ἲᛂ䛾㐍⾜ᛶᅛᙧ䛜䜣 ¾ ᢞ⤒㊰䠖 9 㟼⬦ෆᢞ䛷ᐇ୰ 9 ⤒ཱྀᢞ䛾㏣ຍᐇỴᐃ䠄2015.6䠅 ¾ 㦂ホ౯㡯┠ 9 せホ౯㡯┠䠖Ᏻᛶ䛾☜ㄆ䚸䛚䜘䜃Ᏻ䛺ᢞ㔞䛾☜ㄆ 9 㛵㐃ホ౯㡯┠䠖⸆≀⾑୰⃰ᗘ⸆≀ືែ䛾☜ㄆ䚸⏕≀ᣦᶆ≀㉁䛾᥈ ⣴ホ౯ z ⾑ᾮ䛜䜣䚸ᅛᙧ䛜䜣䠄㞴ᛶ䠅䛾୧᪉䜢ᑐ㇟䛻䚸ᚋ㛤Ⓨ䜢 㐍䜑䛶䛔䛟 ¾ 䜾䝻䞊䝞䝹䛷᭱㐺䛺ሙᡤ䜢㑅䜣䛷㦂䜢ᐇ䛧䚸㛤Ⓨ䜢䛥䜙䛻ຍ㏿䛧䛶䛔䛟 20 MELK䛿᪂つ䛾ᢠ䛜䜣ᶆⓗ䜻䝘䞊䝊 䛜䜣ᖿ⣽⬊䛾⥔ᣢ䛻㧗Ⓨ⌧䛧䛯MELK䛜ᐤ䛧䛶䛔䜛 ⮬ᕫ」〇 OTS167 䛜䜣 ᖿ⣽⬊ ᪤Ꮡ䛾ᢠ䛜䜣⪏ᛶ䛜㧗䛔 ከ䛟䛾䛜䜣⣽⬊ ᪤Ꮡ䛾ᢠ䛜䜣ឤཷᛶ䛜㧗䛔 MELK䛾≉ᚩ z ᪂つᢠ䛜䜣ᶆⓗ䜻䝘䞊䝊䛷䛒䜛䚹 z ᢠ䛜䜣⒪ᚋ䛾Ⓨ䛾ཎᅉ䛾୍䛴䛜䚸䛜䜣ᖿ⣽⬊䛸䛔䜟䜜䚸 OTS167䛿䛜䜣ᖿ⣽⬊䛻᭷ຠ䛷䛒䜛䚹 21 MELK䛿ᵝ䚻䛾䛜䜣✀䛷≉␗ⓗ䛻㐣Ⓨ⌧ z MELK 䛿ᵝ䚻䛾䛜䜣✀䛷㧗⋡䛻≉␗ⓗ䛻㐣Ⓨ⌧䛧䛶䛔䜛 z ⢭ᕢ䜢䛾䛮䛝ṇᖖ⮚ჾ䛷䛾Ⓨ⌧䛿䝊䝻䜎䛯䛿ప䛔 Expression of MELK (cDNA microarray) Tumor type Positive rate (%) Non Small Cell Lung Cancer 100 Small Cell Lung Cancer 100 Bladder Cancer 100 Cholangiocellular Carcinoma 100 Cervical Cancer 93 Lymphoma 93 Breast Cancer 91 Prostate Cancer 86 ColorectalCancer 80 Osteosarcoma 78 CML 77 Positive rate : % of cases where Tumor/Normal > 2 (Data from collaborator (U Tokyo)) 23 normal human organs Northern blot analysis Lin, et al., BCR (2007) 22 MELK䛿ⓑ⾑䛷䜒Ⓨ⌧䛧⏕Ꮡ⋡䛸┦㛵䛩䜛 MELK䛿AML䠄ᛴᛶ㦵㧊ᛶⓑ⾑䠅䛾␗䛺䜛䝃䝤䝉䝑 䝖䛻䜘䛳䛶Ⓨ⌧䝺䝧䝹䛿✀䚻䛾Ỉ‽䛸䛺䛳䛶䛔䜛 㧗䛔䝺䝧䝹䛾MELKⓎ⌧䛿▷䛔⏕Ꮡ⋡䚸 䛚䜘䜃▷䛔↓Ⓨᮇ㛫䛸┦㛵䛧䛶䛔䜛 +LJK ,QWHUPHGLDWH /RZ 7RWDOQ +LJK ,QWHUPHGLDWH /RZ MELK mRNA expression levels in AML patients with different cytogenetic abnormalities. Alachkar, et al., Oncotarget (2014) 23 OTS167㻌 - MELK㜼ᐖάᛶ OTS167 㜼ᐖ᭤⥺ 䖃㻌 MELK䛻ᑐ䛧䛶㧗䛔㜼ᐖάᛶ 䜶䝹䝻䝏䝙䝤䠗 䝍䝹䝉䝞(୰እ)㻌 2 nM (EGFR) 㻌 䝋䝷䝣䜵䝙䝤䠗㻌 䝛䜽䝃䝞䞊䝹䠄䝞䜲䜶䝹䠅 6 nM (c-Raf) 䝇䝙䝏䝙䝤䠗㻌 㻌 䝇䞊䝔䞁䝖䠄䝣䜯䜲䝄䞊䠅 9 nM (VEGFR-2) 㻌 㻌 㻌 䜲䝬䝏䝙䝤䠗㻌 㻌 䜾䝸䝧䝑䜽(䝜䝞䝹䝔䜱䝇) 25 nM (Bcr-Abl) 80 % Inhibition 䞉㻌 IC50* = 1.1 nM 㻌 ᪤䛻ᢎㄆ䛥䜜䛶䛔䜛䜻䝘䞊䝊㜼ᐖ⸆䛾IC50 100 60 40 20 0 10-5 10-4 10-3 10-2 10-1 100 101 102 103 104 105 106 Concentration (nM) 㻌 㻌 㻌 㻌 㻌 㻌 㻌 *䠥䠟50䠗༙ᩘ㜼ᐖ⃰ᗘ䚹ప䛔್䜢♧䛩⛬㜼ᐖ䛸䛧䛶䛾ຠᯝ䛜㧗䛔䛸䛥䜜䜛䚹 䖃㻌 MELKⓎ⌧䛜䜣⣽⬊䛻ᑐ䛧䛶㑅ᢥⓗ䛻᭷ព䛺⣽⬊ቑṪ㜼ᐖάᛶ IC50 = 8.9 nM IC50 = 5.3 nM IC50 = 3.3 nM IC50 = 5.2 nM IC50 = 120.0 nM 䠄⫵䛜䜣⣽⬊䠗MELKⓎ⌧䠅 䠄ங䛜䜣⣽⬊䠗MELKⓎ⌧䠅 䠄䝖䝸䝥䝹䝛䜺䝔䜱䝤ங䛜䜣⣽⬊䠗MELKⓎ⌧䠅 䠄๓❧⭢䛜䜣⣽⬊䠖MELKⓎ⌧䠅 䠄⭤⬔䛜䜣⣽⬊䠗MELK㠀Ⓨ⌧䠅 1.2 Relative cell number A549 T47D DU4475 22Rv1 HT1197 1.0 DU4475 0.8 0.6 0.4 0.2 0.0 0.0001 0.001 0.01 0.1 Compound (PM) ฟ䠖㻌Oncotarget, Chung et al, 2012 1 24 OTS167䛾㜼ᐖάᛶ䠄ⓑ⾑⣽⬊䠅 z OTS167䛿 䛿AML䠄ᛴᛶ㦵㧊ᛶⓑ⾑䠅⣽⬊䛻ᑐ䛧䛶IC50䛷8nM 䡚70nM䛾 㻌 㻌 ⠊ᅖ䛷䚸✀䚻䛾ឤཷᛶ䜢♧䛩 z IC90 䛿䛚䜘䛭100nM䛷䛒䜛 OTS167 In vitro study: AML cells Alachkar, et al., Oncotarget (2014) 25 OTS167䛾ᢠ⭘⒆ຠᯝ䠄MELK≉␗ⓗ䠅 OTS167䛿⏕యෆ䛷䜒MELK≉␗ⓗ䛺ᢠ⭘⒆ຠᯝ A549 䝠䝖⫵䛜䜣⣽⬊⛣᳜䝬䜴䝇 (MELK Ⓨ⌧) PC14 䝠䝖⫵䛜䜣⣽⬊⛣᳜䝬䜴䝇 (MELK No treatment㠀Ⓨ⌧) 䝁䞁䝖䝻䞊䝹䠄ᑐ↷⩌䠅 OTSSP167 10 mg/kg p.o. Q.D. 䝁䞁䝖䝻䞊䝹䠄ᑐ↷⩌䠅 1000 500 400 300 ᭷ព䛺⭘⒆ቑṪ ᢚไຠᯝ䜢ㄆ䜑䜛䠆㻌 200 OTS167 10 mg/kg ⤒ཱྀ1ᅇ/1᪥ ⭘⒆䛾䛝䛥 (mm3) ⭘⒆䛾䛝䛥 (mm3) OTS167 10 mg/kg ⤒ཱྀ1ᅇ/1᪥ 800 600 ⭘⒆ቑṪᢚไຠᯝ ㄆ䜑䜙䜜䛺䛔 400 200 100 0 2 4 6 8 10 12 14 ⒪㛤ጞ᪥䛛䜙䛾᪥ᩘ 䠆⭘⒆ቑṪᢚไຠᯝTumor growth inhibition (TGI): 124 % ฟ䠖㻌Oncotarget, Chung et al, 2012 0 2 4 6 8 10 12 14 ⒪㛤ጞ᪥䛛䜙䛾᪥ᩘ 26 OTS167䛾 䛾ᢠ⭘⒆ຠᯝ䠄㟼⬦ෆᢞ䠅 䝠䝖⫵䛜䜣䠄A549䠅⛣᳜䝬䜴䝇䛷䛾ຠᯝ䚸OTS167㟼⬦ෆᢞ Intravenous administration: once daily (A549 xenograft model) Tumor volume (n = 6) Body weight 1.2 500 TGI=51% 400 300 TGI=91% 200 TGI=108% (p<0.01) 100 0 2 4 6 8 10 12 Relative body weight Tumor volume (mm3) 600 1.1 1 0.9 0.8 14 0 2 Days after initial treatment 4 6 8 10 12 14 Days after initial treatment Vehicle q.d. OTS167 1 mg/kg q.d. OTS167 5 mg/kg q.d. OTS167 10 mg/kg q.d. Paclitaxel 24 mg/kg i.v. Day 0, 3, 7, 10 Paclitaxel 24 mg/kg i.v. Day 0, 1, 2, 3, 4 Chung, et al., Oncotarget (2012) 27 OTS167䛾ᢠ⭘⒆ຠᯝ䠄⤒ཱྀᢞ䠅 䝠䝖⫵䛜䜣䠄A549䠅⛣᳜䝬䜴䝇䛷䛾ຠᯝ䚸OTS167⤒ཱྀᢞ Oral administration: once or twice daily (A549 xenograft model) Tumor volume (n = 6) Body weight 1.2 400 TGI=95% 300 TGI=98% 200 TGI=124% 100 0 2 4 6 8 10 12 Days after initial treatment 14 TGI=126% (p<0.01) Relative body weight Tumor volume (mm3) 500 1.1 1 0.9 0.8 0 2 4 6 8 10 12 14 Days after initial treatment Vehicle q.d. OTS167 2.5 mg/kg b.i.d. OTS167 5 mg/kg b.i.d. OTS167 5 mg/kg q.d. OTS167 10 mg/kg q.d. Paclitaxel 24 mg/kg i.v. Day 0, 3, 7, 10 Paclitaxel 24 mg/kg i.v. Day 0, 1, 2, 3, 4 Chung, et al., Oncotarget (2012) 28 పศᏊ◊✲㛤Ⓨ≧ἣ 䠍䠅MELK㜼ᐖ 㻌 㻌 㻻㼀㻿㻝㻢㻣䠄㻹㻱㻸㻷㜼ᐖ䠅㛤Ⓨ≧ἣ㻌 㻌 㻌 ศᏊᶆⓗ㻹㻱㻸㻷䛾≉㛗㻌 㻌 㻌 㻻㼀㻿㻝㻢㻣䠄㻹㻱㻸㻷㜼ᐖ䠅䛾≉㛗 䠎䠅TOPK㜼ᐖ䠄㠀⮫ᗋヨ㦂୰䠅㻌 㻌 㻌 ศᏊᶆⓗ㼀㻻㻼㻷䛾≉㛗㻌 㻌 㻌 㼀㻻㻼㻷㜼ᐖ䠄㻻㼀㻿㻥㻢㻠➼䠅䛾≉㛗㻌 29 TOPK䛿 䛿᪂つ䛾ᢠ䛜䜣ᶆⓗ䜻䝘䞊䝊 䛜䜣⣽⬊䛾ศᮇ䛻㧗Ⓨ⌧䛧䛯TOPK䛻䜘䜚ศ䛜┒䜣䛸䛺䛳䛶䛔䜛 ⣽⬊ศ㛤ጞ TOPK OTS964➼ p 䝠䝇䝖䞁㻌㻴㻟㻌 p p TOPK p 袼锣菅脟 p p97 p p47 蔧跍议菅脟 TOPK ⣽⬊ศ⤊ TOPK䛾≉ᚩ㻌 z ᪂つᢠ䛜䜣ᶆⓗ䜻䝘䞊䝊䛷䛒䜛䚹 z ⣽⬊ศ㜼ᐖ䜢ᶆⓗ䛸䛩䜛ᢠ䛜䜣䛿᪤䛻ᕷሙ䛻Ꮡᅾ䛧䛶䛔䜛䛜䚸䛭䜜䜙䛿ṇᖖ䛺⣽ ⬊䛾ศ䛻ാ䛔䛶䛔䜛䜻䝘䞊䝊䜢ᶆⓗ䛸䛧䛶䛔䜛䚹୍᪉䚸TOPK䛿䛜䜣⣽⬊≉␗ⓗ䛻㧗 Ⓨ⌧䛧䛶䛜䜣⣽⬊䜢ศ䛥䛫䛶䛔䜛䛾䛷䚸䠰䠫䠬䠧㜼ᐖ䛿స⏝䛜ᑡ䛺䛔䛸⪃䛘䜙䜜䜛䚹 30 TOPK䛿㧗㢖ᗘ䛷ᵝ䚻䛺䛜䜣✀䛻Ⓨ⌧ z TOPK 䛿㧗㢖ᗘ䛷䚸⫵䛜䜣䜔ங䛜䜣䜢ྵ䜐ᵝ䚻䛺䛜䜣✀䛻Ⓨ⌧䛧䛶䛔䜛 z TOPK 䛿⏕Ꮡ䛻ྍḞ䛺ṇᖖ⮚ჾ䛷䛿Ⓨ⌧䛧䛶䛔䛺䛔 Expression of TOPK (cDNA microarray) Tumor type Positive rate (%) Bladder Cancer 100% Cholangiocellular Carcinoma 100% Lung Cancer 100% Cervical Cancer 93% Lymphoma 93% Breast Cancer 91% Prostate Cancer 86% Colorectal Cancer 80% Osteosarcoma 78% CML 77% Breast cancer cell lines Normal organs * *MDA-MB-435 is reported to have been cross-contaminated with is the M14 melanoma line. Northern blot analysis Positive rate : % of cases where Tumor/Normal > 2 (Data from collaborator (U Tokyo)) Park, et al., Can Res (2006) 31 TOPK䛿ᛴᛶ㦵㧊ᛶⓑ⾑䛷䜒Ⓨ⌧䛧䛶䛔䜛 z TOPK was expressed in acute myeloid leukemia as well. AML cell lines AML patients Alachkar, et al., Oncotarget (2015) 32 TOPK≉␗ⓗ㜼ᐖ㻌 䠉㻌 OTS964㻌 ➼㻌 䠉 OTS䠕䠒䠐䛜䚸䛜䜣⣽⬊ศ䜢ᙉ䛟㜼ᐖ䛩䜛 OTS964䛺䛧 OTS964䛒䜚 HP䛻 䛻䛾䛳䛶䛔䜛 ⣽⬊ศ䛾ື⏬ HP䛻䛾䛳䛶䛔䜛 ⣽⬊ศ䛾ື⏬ 33 ฟ䠖㻌Sci Transl Med 22 October 2014: Vol. 6, Issue 259, p. 259ra145 OTS964䠄⤒ཱྀᢞ䠅䛾ᢠ⭘⒆ຠᯝ OTS964䛿⤒ཱྀᢞ䛷䝬䜴䝇䠒༉䛩䜉䛶䛾䛜䜣䜢ᾘኻ 䠄᭷ព䛺ᢠ⭘⒆ຠᯝ䠅 9 㻌 LU99䠄䝠䝖⫵䛜䜣⣽⬊䠅䜢⛣᳜䛧䛯䝬䜴䝇(6༉) 9 㻌 ẖ᪥1ᅇ䚸ィ14ᅇ䚸OTS964 100mg/kg ⤒ཱྀᢞ ⭘⒆䛾䛝䛥 య㔜 ࢥࣥࢺ࣮ࣟࣝ㸦ᑐ↷⩌㸧 ࢱ࢟ࢯ࣮ࣝ 24 mg/kg 㟼ὀ 0, 3, 7, 10᪥ OTS964 100 mg/kg ⤒ཱྀ 1ᅇ/1᪥ 1.3 ࢱ࢟ࢯ࣮ࣝ 24 mg/kg 㟼ὀ 0, 3, 7, 10᪥ 1500 1.2 య㔜ẚ ⭘⒆ࡢࡁࡉ (mm3) ࢥࣥࢺ࣮ࣟࣝ㸦ᑐ↷⩌㸧 OTS964 100 mg/kg ⤒ཱྀ 1ᅇ/1᪥ 2000 1000 500 1.1 1 0.9 0 0 7 14 21 ⒪㛤ጞࡽࡢ⤒㐣᪥ᩘ 䠒༉୰䠒༉䛷⭘⒆ᾘኻ ฟ䠖㻌Sci Transl Med, Matsuo et al, 2014 , ♫ෆ㈨ᩱ 28 0 7 14 21 28 ⒪㛤ጞࡽࡢ⤒㐣᪥ᩘ స⏝䠄య㔜ῶᑡ䠅ೃ䛺䛧 34 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠍䠅⭘⒆ච䛸䝀䝜䝮 䠎䠅TCRゎᯒ䛾ᴗ 䠏䠅㑇ఏᏊゎᯒ䝕䞊䝍䛻䜒䛸䛵䛟䚸㻌 㻌 㻌 ⏬ᮇⓗ䛺ච⒪ἲ䛾㛤Ⓨ䠄䠙ಶู་⒪䠅㻌 35 ⭘⒆ච䛸䝀䝜䝮䠄1/䠐䠅 • DNAಟ㑇ఏᏊ␗ᖖ䛷㉳䛣䜛㑇ఏᛶ⭠䛜䜣䛿䚸୍⯡ⓗ䛺 ⭠䛜䜣䛸ẚ䜉䛶ணᚋ䛾Ⰻ䛔䛣䛸䛜⣙20ᖺ๓䛻ሗ࿌䛥䜜䛶䛔䜛 э㻌 䛣䛾䛜䜣䛸㑇ఏᏊኚ␗䛾㛵ಀ䛛䜙䚸 㻌 ᭷ຠ䛺䛜䜣⒪䛾௬ㄝ䛜⪃䛘䜙䜜䜛 http://yusukenakamura.hatenablog.com/entry/2015/02/15/131903 36 ⭘⒆ච䛸䝀䝜䝮䠄䠎/䠐䠅 http://yusukenakamura.hatenablog.com/entry/2015/02/14/053418 37 ⭘⒆ච䛸䝀䝜䝮䠄䠏/䠐䠅 䛜䜣⣽⬊䛷䛾㑇ఏᏊ␗ᖖ䛜ከ䛔䛸ච䜢ᙉ䛟άᛶ䛩䜛 http://yusukenakamura.hatenablog.com/entry/2015/02/14/053418 38 ⭘⒆ච䛸䝀䝜䝮䠄䠐/䠐䠅 http://yusukenakamura.hatenablog.com/entry/2015/02/15/131903 39 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠎䠅TCRゎᯒ䛾ᴗ 㻌 ୖ༙ᮇ䛾‽ഛᮇ㛫䜢⤒䛶䚸㻥᭶䛻㼀㻯㻾ゎᯒ䛾ୖ䜢ィୖ㻌 㻌 ᏛⓎ⾲䜔㻮㼕㼛㻶㼍㼜㼍㼚䛾䝷䞁䝏䝵䞁䝉䝭䝘䞊䛷ၨⵚάື㻌 㻌 䜎䛪䛿䚸䛜䜣䛾◊✲⪅䜢୰ᚰ䛻ཷὀ䜢ணᐃ㻌 㻌 䛭䛾ᚋ䚸䛜䜣௨እ䛾㡿ᇦ䜔〇⸆♫䛾◊✲䜈ᣑぢ㎸㻌 㻌 䠏䠅㑇ఏᏊゎᯒ䝕䞊䝍䛻䜒䛸䛵䛟䚸㻌 㻌 㻌 ⏬ᮇⓗ䛺ච⒪ἲ䛾㛤Ⓨ䠄䠙ಶู་⒪䠅㻌 40 TCRゎᯒ㻌 →㻌 䛜䜣ච⒪ἲ䛾ㄢ㢟ゎỴ z ච䝰䝙䝍䝸䞁䜾 㻌 㻌 ⒪䛻䜘䜛ච≧ែ䛾ኚ䜢ᫎ䛩䜛䛂デ デ᩿䛾ᣦᶆ䠄TCRゎᯒ)䛃䛾☜❧ 㻌 㻌 㻌 䚓 ㎿㏿䛷ᐃ㔞ⓗ䛺⒪ἲ䛾ホ౯䛻䜘䜚䚸⒪⥅⥆/୰Ṇ䛾ุ᩿䛜ⓗ☜䛻 ⒪๓ z ᝈ⪅㑅ᢥ 㻌 ⮫ᗋຠᯝ䛾๓ண 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 ⒪ᚋ ⭘⒆⦰ᑠ 䞉⒪๓䛻T⣽⬊☜ㄆ 㻌 㻌 →㻌 䛜䜣ච⒪㛤ጞ 䞉⒪๓䛻T⣽⬊䛺䛧 㻌 㻌 →㻌 䛜䜣ච⒪ᅇ㑊 ⭘⒆ቑ 㻌 㻌 㻌 䚓 ዌຠ⋡䛾ୖ᪼ 㻌 㻌 㻌 㻌 㻌 ⒪㛤ጞ䛾ุ᩿ ᢠཎA≉␗ⓗT⣽⬊ ᢠཎB≉␗ⓗT⣽⬊ 41 TCRゎ ゎᯒ䛾ά⏝ 䛜䜣䛾㑇ఏᏊኚ␗䛸TCRከᵝᛶ (a)㻌 (b)㻌 ) (c) (c)㻌 (Choudhury, et al. European Urology Focus 2015, in press) 䠆㻺㼑㼛㼑㼜㼕㼠㼛㼜㼑䠖㑇ఏᏊኚ␗⏤᮶䛷䛜䜣⣽⬊䛾⾲㠃䛻ᥦ♧䛥䜜䛖䜛䝨䝥䝏䝗㻌 ฟ䠖䝅䜹䝂Ꮫ୰ᮧᩍᤵ䛻䜘䜛䝞䜲䜸䝆䝱䝟䞁2015䝷䞁䝏䝵䞁䝉䝭䝘䞊 42 Immunopharmacogenomics䛻䜘䜛᪂䛧䛔䛜䜣⒪ ච䝞䝷䞁䝇䛸ᝈ 㻌 (f)㻌 (g)㻌 43 ฟ䠖䝅䜹䝂Ꮫ୰ᮧᩍᤵ䛻䜘䜛䝞䜲䜸䝆䝱䝟䞁2015䝷䞁䝏䝵䞁䝉䝭䝘䞊 ┠ḟ 䠍䠅ᢠ䛜䜣䝬䞊䜿䝑䝖䛾ᴫἣ 䠎䠅OTS䛾≉㛗䛸⤒Ⴀ᪉㔪 䠏䠅◊✲㛤Ⓨ䝟䜲䝥䝷䜲䞁䛸ᙜᮇ䛾άື 䠐䠅◊✲㛤Ⓨ䛾㐍ᤖ≧ἣ 㻌 పศᏊ◊✲㛤Ⓨ≧ἣ 㻌 ಶู་⒪䜈䛾ྲྀ䜚⤌䜏 䠑䠅㈨ᩱ㞟 44 OTSA101䛿⭷⫗⭘䛻ᑐ䛩䜛ᢠయ་⸆㻌 ৭੦؟ ⭷⫗⭘䛻㧗㢖ᗘ䛻㧗Ⓨ⌧䛧䛶䛔䜛 ṇᖖ⤌⧊䛻䛿Ⓨ⌧䛧䛶䛔䛺䛔 ⭷⫗⭘䛾⣽⬊ቑṪ䛻㛵䛧䛶䛔䜛 ఏ؟ Frizzled Homologue 10 (FZD10) 7Ⴭฮৢঞ७উॱش 45 㻻㼀㻿㻭㻝㻜㻝䛾ᢠ⭘⒆ຠᯝ㻌 䠍ᅇ䛾ᢞ䛷ከ䛟䛾䝬䜴䝇䛷⭘⒆䛜ᾘኻ䠄᭷ព䛺ຠᯝ䠅 䝠䝖⭷⫗⭘⣽⬊(SYO-1)䜢⛣᳜䛧䛯䝬䜴䝇 90Yقॖॵॺজक़ك ⒪㛤ጞᖹᆒ⭘⒆య✚260mm3 ⭘⒆య✚ẚ⋡ 25 ؟50 uCiؚಯဿଖ 䝁䞁䝖䝻䞊䝹 (5༉) 20 90Yᶆ㆑䝠䝖IgGᢠయ(5༉) 㠀ᶆ㆑ᢠFDZ10 ᢠయ(5༉) 15 10 90Yᶆ㆑ᢠFZD10ᢠయ(OTSA101) (30༉) 5 0 0 10 ༢ᅇᢞ ฟ䠖AACR/JCA Joint Conference, 2010䠈㻌 ♫ෆ㈨ᩱ 20 30 40 50 60 ᪥ 46 㻻㼀㻿㻭㻝㻜㻝㻌⮫ᗋ㛤Ⓨ≧ἣ䛸ᚋ䛾᪉㔪㻌 䝣䝷䞁䝇䛻䛚䛔䛶⭷⫗⭘ᝈ⪅䜢ᑐ㇟䛸䛧䛯➨䊠┦㻌 㻌 㻌⮫ᗋヨ㦂䛜㐍⾜୰㻌 9 䝆䝱䞁䠙䜲䞂䞉䝤䝺㻯㻸㻮ᩍᤵ䞉䝉䞁䝍䞊㛗㻌䠄ඖḢᕞ䛜䜣◊✲䞉⒪ᶵᵓ㛗䠅ᑟ㻌 9 㻯㼍㼚㼏㽴㼞㼛㼜㽿㼘㼑㻌㻸㼥㼛㼚㻌㻭㼡㼢㼑㼞㼓㼚㼑㻌㻾㼔㽿㼚㼑㻙㻭㼘㼜㼑㼟㻩㻯㻸㻭㻾䛻䜘䜛◊✲㈝ຓᡂ㻌 Ḣᕞ་⸆ရᗇ䠄㻱㻹㻭䠅䚸⡿㣗ရ་⸆ရᒁ䠄䠢䠠䠝䠅䛻䜘䜛 䜸䞊䝣䜯䞁䝗䝷䝑䜾ᣦᐃ᥎ዡ່࿌䜢ཷ䛡䛯㻌 ⭷⫗⭘䛻䛚䛡䜛ᢎㄆ⏦ㄳ䠄Ḣ⡿䠅䜢┠ᣦ䛩㻌 9 ➨䊠┦⮫ᗋヨ㦂䛾⤖ᯝ䛻ᇶ䛵䛝㻱㻹㻭㻛㻲㻰㻭䛸ḟ┦⮫ᗋヨ㦂䜢᳨ウ䛩䜛㻌 㻌 㻌 䠄䜸䞊䝣䜯䞁䝗䝷䝑䜾ᣦᐃά⏝䠅㻌 9 ḟ┦⮫ᗋヨ㦂䛿Ḣ⡿䜢ᑐ㇟䛻䚸ᢎㄆ⏦ㄳ䠄䠪䠠䠝䠅䛻ᚲ㡲䛾⮫ᗋヨ㦂䛸䛧䚸ḟ┦⮫ ᗋヨ㦂⤊ᚋ䛾ᢎㄆ⏦ㄳ䜢┠ᣦ䛩 䝁䞁䝟䝙䜸䞁デ᩿⸆䜢㛤Ⓨ䛧䚸䛾䛜䜣✀䛾㏣ຍ㐺ᛂ 䜢᳨ウ䛩䜛㻌 47 ᮏ㈨ᩱ䛿䚸ᢞ㈨⪅䛻ᑐ䛩䜛ሗᥦ౪䜢┠ⓗ䛸䛧䛶グ㍕䛧䛯䜒䛾 䛷䛒䜚䚸ᢞ㈨່ㄏ䜢┠ⓗ䛸䛧䛯䜒䛾䛷䛿䛒䜚䜎䛫䜣䚹ᮏ㈨ᩱⓎ⾲ ᪥⌧ᅾ䛾ᑗ᮶䛻㛵䛩䜛๓ᥦ䚸ぢ㏻䛧䚸ィ⏬䛻ᇶ䛵䛟ண 䛜ྵ䜎 䜜䛶䛚䜚䜎䛩䚹䛣䜜䜙䛿⌧Ⅼ䛷ධᡭྍ⬟䛺ሗ䛛䜙ᚓ䜙䜜䛯 ᙜ♫䛾ุ᩿䛻ᇶ䛵䛟䜒䛾䛷䛒䜚䚸ᚋ䛾⤒῭ໃ䚸ᕷሙ䛾ኚື ➼䛻㛵䜟䜛䝸䝇䜽䜔☜ᐃせᅉ䛻䜘䜚䚸ᐇ㝿䛾ᴗ⦼䛿ண 䛸 䛝䛟␗䛺䜛ྍ⬟ᛶ䛜䛒䜚䜎䛩䚹 ᙜ♫䛾ᴗィ⏬䛻ᑐ䛩䜛ホ౯ཬ䜃ᢞ㈨䛻㛵䛩䜛Ỵᐃ䛿ᢞ㈨⪅ 䛤⮬㌟䛾ุ᩿䛻䛚䛔䛶⾜䜟䜜䜛䜘䛖䛚㢪䛔䛔䛯䛧䜎䛩䚹 48
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