JPWO2017142083A1 - エクソソームの遺伝子機能を抑制することができる複合体、がんの増殖及び/又は転移抑制剤 - Google Patents
エクソソームの遺伝子機能を抑制することができる複合体、がんの増殖及び/又は転移抑制剤 Download PDFInfo
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- JPWO2017142083A1 JPWO2017142083A1 JP2018500234A JP2018500234A JPWO2017142083A1 JP WO2017142083 A1 JPWO2017142083 A1 JP WO2017142083A1 JP 2018500234 A JP2018500234 A JP 2018500234A JP 2018500234 A JP2018500234 A JP 2018500234A JP WO2017142083 A1 JPWO2017142083 A1 JP WO2017142083A1
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Abstract
Description
項1. エクソソーム表面抗原を標的とする抗体又は抗体断片と遺伝子又はその発現産物の抑制剤を含む複合体であって、前記抗体又は抗体断片と前記遺伝子又はその発現産物の抑制剤は直接又はリンカーを介して共有結合するか、或いは、非共有結合的に結合している、複合体。
項2. エクソソーム表面抗原がCD9、CD63、CD81又はCD147である、項1に記載の複合体。
項3. 前記抗体又は抗体断片はシステイン、アルギニン、リシン及びオルニチンからなる群から選ばれる少なくとも1種のアミノ酸を含むペプチドで修飾され、前記遺伝子又はその発現産物の抑制剤は前記ペプチドと共有結合(S−S結合)、配位結合又は非共有結合的に結合してなる、項1又は2に記載の複合体。
項4. 前記ペプチドは、グリシン又はアラニンをさらに含む、項3に記載の複合体。
項5. 前記ペプチドは、ポリリシン又はポリアルギニンである、項3に記載の複合体。
項6. 前記ペプチドがポリアルギニンである、項5に記載の複合体。
項7. 前記遺伝子又はその発現産物の抑制剤は抗miRNA核酸であり、前記抗miRNA核酸はエクソソームに含まれるmiRNAと相補鎖を形成することでmiRNAの機能を抑制する核酸である、項1〜6のいずれか1項に記載の複合体。
項8. 前記抗体又は抗体断片が抗CD63抗体である、項1に記載の複合体。
項9. 前記遺伝子又はその発現産物の抑制剤がエクソソーム中に存在するmiRNA又は遺伝子の抑制剤である、項1に記載の複合体。
項10. 遺伝子又はその発現産物の抑制剤がmiRNA抑制剤である、項1に記載の複合体。
項11. 前記抗体又は抗体断片がモノクローナル抗体、一本鎖抗体、Fab、Fab'、F(ab')2、Fv又はscFvである、項1に記載の複合体。
項12. 項1〜11のいずれか1項に記載の複合体を含む、がんの増殖及び/又は転移抑制剤。
抗体又は抗体断片(1)と化合物(2)を反応させてアミジン化合物(3)とし、これと化合物(4)を反応させてペプチド或いは遺伝子又はその発現産物の抑制剤が結合した抗体又は抗体断片(5)を得ることができる。ペプチド或いは遺伝子又はその発現産物の抑制剤が結合した抗体又は抗体断片(5)を得るための具体的な反応条件は、ACS Chem. Biol. 2011, 6, 962-970などの記載を参考にして当業者は容易に決定することができる。上記のスキーム1は単なる例示であり、ペプチド或いは遺伝子又はその発現産物の抑制剤が抗体又は抗体断片に直接もしくは適当なリンカーを介して共有結合している限り、全て本発明に含まれる。
エクソソーム表面抗原を認識する抗体が、エクソソームとともに細胞内に取り込まれるかどうかを検証した。
エクソソーム表面抗原を認識する抗体が、エクソソームとともに細胞内に取り込まれるかどうかを検証した。
anti-CD63抗体/ anti-miR核酸複合体が細胞内に取り込まれた後、microRNA機能阻害効果を発揮するかどうかを評価した。
anti-CD63抗体/ anti-miR核酸複合体がエクソソーム内包型microRNAに対する機能阻害効果を発揮するかどうかを評価した。
anti-CD63抗体/ anti-miR21核酸複合体がin vivoにおいてもmicroRNAに対する機能阻害効果を発揮するかどうかを評価した。
Claims (12)
- エクソソーム表面抗原を標的とする抗体又は抗体断片と遺伝子又はその発現産物の抑制剤を含む複合体であって、前記抗体又は抗体断片と前記遺伝子又はその発現産物の抑制剤は直接又はリンカーを介して共有結合するか、或いは、非共有結合的に結合している、複合体。
- エクソソーム表面抗原がCD9、CD63、CD81又はCD147である、請求項1に記載の複合体。
- 前記抗体又は抗体断片はシステイン、アルギニン、リシン及びオルニチンからなる群から選ばれる少なくとも1種のアミノ酸を含むペプチドで修飾され、前記遺伝子又はその発現産物の抑制剤は前記ペプチドと共有結合(S−S結合)、配位結合又は非共有結合的に結合してなる、請求項1又は2に記載の複合体。
- 前記ペプチドは、グリシン又はアラニンをさらに含む、請求項3に記載の複合体。
- 前記ペプチドは、ポリリシン又はポリアルギニンである、請求項3に記載の複合体。
- 前記ペプチドがポリアルギニンである、請求項5に記載の複合体。
- 前記遺伝子又はその発現産物の抑制剤は抗miRNA核酸であり、前記抗miRNA核酸はエクソソームに含まれるmiRNAと相補鎖を形成することでmiRNAの機能を抑制する核酸である、請求項1〜6のいずれか1項に記載の複合体。
- 前記抗体又は抗体断片が抗CD63抗体である、請求項1に記載の複合体。
- 前記遺伝子又はその発現産物の抑制剤がエクソソーム中に存在するmiRNA又は遺伝子の抑制剤である、請求項1に記載の複合体。
- 遺伝子又はその発現産物の抑制剤がmiRNA抑制剤である、請求項1に記載の複合体。
- 前記抗体又は抗体断片がモノクローナル抗体、一本鎖抗体、Fab、Fab'、F(ab')2、Fv又はscFvである、請求項1に記載の複合体。
- 請求項1〜11のいずれか1項に記載の複合体を含む、がんの増殖及び/又は転移抑制剤。
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Title |
---|
FIORI, M. E. ET AL.: "Antitumor effect of miR-197 targeting in p53 wild-type lung cancer", CELL DEATH AND DIFFERENTIATION, vol. 21, no. 5, JPN6017011705, 2014, pages 774 - 782, XP055410574, ISSN: 0004695507, DOI: 10.1038/cdd.2014.6 * |
SWEENY, L. ET AL.: "A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma", ORAL ONCOLOGY, vol. 49, no. 10, JPN6021012664, 2013, pages 991 - 997, XP055152770, ISSN: 0004695508, DOI: 10.1016/j.oraloncology.2013.07.006 * |
XIONG, B. ET AL.: "MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorect", INTERNATIONAL JOURNAL OF ONCOLOGY, vol. 42, no. 1, JPN6017011702, 2013, pages 219 - 228, XP055410573, ISSN: 0004695506, DOI: 10.3892/ijo.2012.1707 * |
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