JP2015526446A - 幹細胞増強治療法 - Google Patents
幹細胞増強治療法 Download PDFInfo
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3076—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
- C07K16/3092—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties against tumour-associated mucins
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Abstract
Description
(i) その配列が、SEQ ID NOS:1-11の配列をもつペプチドのうちのいずれかであるペプチドを認識する抗体の混合セットの生成;
(ii) SEQ ID NO:4、SEQ ID NO:5、あるいはSEQ ID NO:6のペプチドに、しかしSEQ ID NO:3;のペプチドにではない、結合する抗体を選択すること;
(iii)表面上に吸着された時、幹細胞の付着を促進する抗体を選択すること;
(iv)また、癌細胞に影響なしで、二価の形式で、幹細胞の成長を刺激し、および一価の形式で、肝細胞の成長を阻害する抗体を選択すること。
あるいは、抗体は、SEQ ID NO:5のペプチド、SEQ ID NO:6のペプチド、又は結合したSEQ ID NOS:4と5からの連続するアミノ酸を含んでいるペプチドに結合する。さらにより好適な実施態様では、幹細胞抗体のセットに属する抗体は、MUC1陽性の癌細胞にではなくヒトの幹および/または先祖細胞に結合する。さらに、幹細胞抗体セットに属する抗体は、それらが二価の場合に幹および/または先祖細胞増殖を刺激し、かつ一価の場合(例えば、Fab)に、幹および/または先祖細胞増殖を阻害しうるそれらの能力によって選択される。まだもっと好適な実施態様では、二価型の抗体も一価型の抗体も癌細胞の成長に影響しない。
(SEQ ID NO: 12) MIN-C2重鎖可変領域。
(SEQ ID NO: 13) MIN-C2重鎖可変領域。
(SEQ ID NO: 14) MIN-C2カッパ鎖可変領域。
(SEQ ID NO: 15) MIN-C2カッパ鎖可変領域。
(SEQ ID NO: 16) MIN-E6重鎖-7可変領域。
(SEQ ID NO: 17) MIN-E6重鎖-7可変領域。
(SEQ ID NO: 18) MIN-E6重鎖-8可変領域。
(SEQ ID NO: 19) MIN-E6重鎖-8可変領域。
(SEQ ID NO: 20) MIN-E6カッパ鎖可変領域。
(SEQ ID NO: 21) MIN-E6カッパ鎖可変領域。
(SEQ ID NO: 22) MIN-C2Fab重鎖。
(SEQ IDNO: 23) MIN-C2Fabカッパ鎖。
(SEQ ID NO: 24) MIN-C2Fab重鎖。
(SEQ IDNO: 25) MIN-C2Fabカッパ鎖。
(SEQ IDNO: 26) MIN-C2軽CL領域アミノ酸配列。
(SEQ IDNO: 27) MIN-C2重鎖CH1領域アミノ酸配列。
(SEQ ID NO: 28) MIN-C2軽鎖可変フレームワーク領域1(FWR1)アミノ酸配列。
(SEQ ID NO: 29) MIN-E6軽鎖可変フレームワーク領域1(FWR1)アミノ酸配列。
(SEQ ID NO: 30) MIN-C2軽鎖可変相補性決定領域1(CDR1)アミノ酸配列。
(SEQ ID NO: 31) MIN-E6軽鎖可変相補性決定領域1(CDR1)。
(SEQ ID NO: 32) MIN-C2軽鎖可変フレームワーク領域2(FWR2)アミノ酸配列。
(SEQ ID NO: 33) MIN-E6軽鎖可変フレームワーク領域2(FWR2)アミノ酸配列。
(SEQ ID NO: 34) MIN-C2軽鎖可変相補性決定領域2(CDR2)アミノ酸配列。
(SEQ ID NO: 35) MIN-E6軽鎖可変相補性決定領域2(CDR2)アミノ酸配列。
(SEQ ID NO: 36) MIN-C2軽鎖可変フレームワーク領域3(FWR3)アミノ酸配列。
(SEQ ID NO: 37) MIN-E6軽鎖可変フレームワーク領域3(FWR3)アミノ酸配列。
(SEQ ID NO: 38) MIN-C2軽鎖可変相補性決定領域3(CDR3)アミノ酸配列。
(SEQ ID NO: 39) MIN-E6軽鎖可変相補性決定領域3(CDR3)アミノ酸配列。
(SEQ ID NO: 40) MIN-C2重鎖可変フレームワーク領域1(FWR1)アミノ酸配列。
(SEQ ID NO: 41) MIN-E6-7重鎖可変フレームワーク領域1(FWR1)アミノ酸配列。
(SEQ ID NO: 42) MIN-E6-8重鎖可変フレームワーク領域1(FWR1)アミノ酸配列。
(SEQ ID NO: 43) MIN-C2重鎖可変相補性決定領域1(CDR1)アミノ酸配列。
(SEQ ID NO: 44) MIN-E6-7重鎖可変相補性決定領域1(CDR1)アミノ酸配列。
(SEQ ID NO: 45) MIN-E6-8重鎖可変相補性決定領域1(CDR1)アミノ酸配列。
(SEQ ID NO: 46) MIN-C2重鎖可変フレームワーク領域2(FWR2)アミノ酸配列。
(SEQ ID NO: 47) MIN-E6-7重鎖可変フレームワーク領域2(FWR2)アミノ酸配列。
(SEQ ID NO: 48) MIN-E6-8重鎖可変フレームワーク領域2(FWR2)アミノ酸配列。
(SEQ ID NO: 49) MIN-C2重鎖可変相補性決定領域2(CDR2)アミノ酸配列。
(SEQ ID NO: 50) MIN-E6-7重鎖可変相補性決定領域2(CDR2)アミノ酸配列。
(SEQ ID NO: 51) MIN-E6-8重鎖可変相補性決定領域2(CDR2)アミノ酸配列。
(SEQ ID NO: 52) MIN-C2重鎖可変フレームワーク領域3(FWR3)アミノ酸配列。
(SEQ ID NO: 53) MIN-E6-7重鎖可変フレームワーク領域3(FWR3)アミノ酸配列。
(SEQ ID NO: 54) MIN-E6-8重鎖可変フレームワーク領域3(FWR3)アミノ酸配列。
(SEQ ID NO: 55) MIN-C2重鎖可変相補性決定領域3(CDR3)アミノ酸配列。
(SEQ ID NO: 56) MIN-E6-7重鎖可変相補性決定領域3(CDR3)アミノ酸配列。
(SEQ ID NO: 57) MIN-E6-8重鎖可変相補性決定領域3(CDR3)アミノ酸配列。
(SEQ ID NO: 58) IGHV3(Igblastからの名前)。:
FWR1: MIN-C2の可変重鎖領域への84.7%相同性(249/294)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 59) IGHV3(Igblastからの名前)。:
FWR2: MIN-C2の可変重鎖領域への84.7%相同性(249/294)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 60) IGHV3(Igblastからの名前)。:
FWR3: MIN-C2の可変重鎖領域への84.7%相同性(249/294)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 61) IGkV7(Igblastからの名前)。:
FWR1: MIN-C2の可変軽鎖領域への76.4%相同性(226/296)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 62) IGkV7(Igblastからの名前)。:
FWR2: MIN-C2の可変軽鎖領域への76.4%相同性(226/296)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 63) IGkV7(Igblastからの名前)。:
FWR 3: MIN-C2の可変軽鎖領域への76.4%相同性(226/296)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 64) IGHV3(Igblastからの名前)。:
FWR1: MIN-E6の可変重鎖領域への84.1%相同性(249/296)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 65) IGHV3(Igblastからの名前)。:
FWR2: MIN-E6の可変重鎖領域への84.1%相同性(249/296)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 66) IGHV3(Igblastからの名前)。:
FWR3: MIN-E6の可変重鎖領域への84.1%相同性(249/296)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 67) IGkV3(Igblastからの名前)。:
FWR1: MIN-E6の可変軽鎖領域への69.5%相同性(187/269)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 68) IGkV3(Igblastからの名前)。:
FWR2: MIN-E6の可変軽鎖領域への69.5%相同性(187/269)を備えたヒトのIgG抗体フレームワーク領域配列。
(SEQ ID NO: 69) IGkV3(Igblastからの名前)。:
FWR3: MIN-E6の可変軽鎖領域への69.5%相同性(187/269)を備えたヒトのIgG抗体フレームワーク領域配列。
Claims (18)
- 患者の幹細胞への刺激によって利益を得る患者を治療する方法であって、ヒトの未分化幹細胞で発現されたMUC1タンパク質のエピトープに特異的に結合する抗体を患者に投与することを含む、方法。
- 抗体は、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:9、SEQ ID NO:10あるいはSEQ ID NO:11のペプチドの少なくとも6つの連続したアミノ酸に特異的に結合する、請求項1に記載の方法。
- 抗体は、SEQ ID NO:3、SEQ ID NO:7あるいはSEQ ID NO:8のペプチドに、結合しないか、実質的に殆ど結合しない、請求項1に記載の方法。
- 患者が、癌である、請求項1に記載の方法。
- 患者は、癌であり、化学療法または放射線を受けている、請求項4に記載の方法。
- 患者は、慢性腎臓病である、請求項1に記載の方法。
- 癌患者又は癌発症リスクのある患者の処置法であって、癌細胞で発現するがヒトの未分化幹細胞では発現しないMUC1タンパク質のエピトープに特異的に結合する抗体を患者に投与することを含む方法。
- 抗体は、SEQ ID NO:3のペプチドに特異的に結合するが、SEQ ID NO:4のペプチドに結合しないか、実質的に殆ど結合しない、請求項7に記載の方法。
- 一価の癌細胞特異的抗体を患者に投与することを含む、MUC1陽性の癌と診断された患者を処置する方法。
- 癌細胞特異抗体は、SEQ ID NO:3のペプチドに特異的に結合するが、SEQ ID NO:4のペプチドに結合しないか、実質的に殆ど結合しない、請求項9に記載の方法。
- 一価の癌細胞特異抗体および二価の幹細胞特異抗体を患者に投与することを含む、MUC1陽性の癌と診断された患者を処置する方法。
- 癌細胞特異抗体は、SEQ ID NO:3のペプチドに特異的に結合するが、SEQ ID NO:4のペプチドに結合しないか、実質的に殆ど結合しない、請求項11に記載の方法。
- 幹細胞特異抗体が、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:9、SEQ ID NO:10あるいはSEQ ID NO:11のペプチドの少なくとも6つの連続したアミノ酸に特異的に結合するが、EQ ID NO:3、SEQ ID NO:7あるいはSEQ ID NO:8のペプチドに結合しないか、実質的に殆ど結合しない、請求項11に記載の方法。
- 癌細胞の増殖をおこすことなしに、ヒト幹細胞で発現するMUC1タンパク質のエピトープに特異的に結合する抗体との接触を含む、幹又は先祖細胞を増殖させる方法。
- 抗体は、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:9、SEQ ID NO:10あるいはSEQ ID NO:11のペプチドの少なくとも6つの連続したアミノ酸に特異的に結合する、請求項14に記載の方法。
- 抗体は、SEQ ID NO:3、SEQ ID NO:7あるいはSEQ ID NO:8のペプチドに結合しないか、実質的に殆ど結合しない、請求項15に記載の方法。
- 次のステップを含む、幹細胞に特異的に結合するが、癌細胞には結合しない抗体を得る方法:
(i) その配列が、SEQ ID NOS:1-11の配列をもつペプチドのいずれかであるペプチドを認識する抗体の混合セットの生成;
(ii) SEQ ID NO:4、SEQ ID NO:5、あるいはSEQ ID NO:6のペプチドに結合するが、SEQ ID NO:3のペプチドには結合しない抗体を選択すること;
(iii)表面に吸着されたとき、幹細胞の付着を促進する抗体を選択すること;
(iv)癌細胞になんらの影響なしに、二価型で幹細胞の成長を刺激し、一価型で幹細胞の成長を阻害する抗体を選択する。 - 次のステップを含む、癌細胞に特異的に結合するが、幹細胞には結合しない抗体を得る方法:
(i) その配列が、SEQ ID NOS:1-11の配列をもつペプチドのいずれかであるペプチドを認識する抗体の混合セットの生成;
(ii) SEQ ID NO:3のペプチドに結合するが、SEQ ID NO:4、SEQ ID NO:5、あるいはSEQ ID NO:6のペプチドには結合しない抗体を選択すること;
(iii)表面に吸着されたとき、癌細胞の付着を促進する抗体を選択すること;
(iv)幹細胞になんらの影響なしに、二価型で癌細胞の成長を刺激し、一価型で癌細胞の成長を阻害する抗体を選択する。
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CA2976089A1 (en) * | 2015-02-10 | 2016-08-18 | Minerva Biotechnologies Corporation | Humanized anti-muc1* antibodies |
WO2017177199A2 (en) * | 2016-04-08 | 2017-10-12 | Iti Health, Inc. | Plectin-1 binding antibodies and uses thereof |
WO2018187512A1 (en) * | 2017-04-04 | 2018-10-11 | Corvus Pharmaceuticals, Inc. | Methods for treating cd73hi tumors |
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