RU2015117237A - Химерные антигенные рецепторы м971 - Google Patents
Химерные антигенные рецепторы м971 Download PDFInfo
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Abstract
1. Химерный антигенный рецептор (CAR), содержащий антигенсвязывающий домен, содержащий аминокислотные последовательности SEQ ID NO 1-6, трансмембранный домен и внутриклеточный домен Т-клеточного сигналинга.2. CAR по п. 1, где антигенсвязывающий домен содержит вариабельную область легкой цепи, содержащую аминокислотную последовательность, включающую SEQ ID NO 7.3. CAR по п. 1 или 2, где антигенсвязывающий домен содержит вариабельную область тяжелой цепи, содержащую аминокислотную последовательность, включающую SEQ ID NO 8.4. CAR по п. 1 или 2, где антигенсвязывающий домен содержит аминокислотную последовательность, включающую SEQ ID NO 9.5. CAR по п. 1 или 2, где антигенсвязывающий домен содержит линкер, включающий SEQ ID NO 11.6. CAR по п. 1 или 2, дополнительно содержащий лидерную последовательность, включающую SEQ ID NO 10.7. CAR по п. 1 или 2, где трансмембранный домен содержит i) часть CD8 и/или ii) часть CD28.8. CAR по п. 1 или 2, где трансмембранный домен содержит аминокислотную последовательность, включающую SEQ ID NO 12 или 18, и/или аминокислотную последовательность, включающую SEQ ID NO 15.9. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит один или более чем один из i) внутриклеточной части сигналинга CD28, ii) внутриклеточной части сигналинга CD137 и iii) внутриклеточной части сигналинга CD3 дзета.10. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит аминокислотную последовательность, включающую последовательность SEQ ID NO 16 или 19.11. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит аминокислотную последовательность, включающую SEQ ID NO 13 или 20.12. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит аминокислотную последовательность, включающую SEQ ID NO 14, 17 или 21.13. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит
Claims (31)
1. Химерный антигенный рецептор (CAR), содержащий антигенсвязывающий домен, содержащий аминокислотные последовательности SEQ ID NO 1-6, трансмембранный домен и внутриклеточный домен Т-клеточного сигналинга.
2. CAR по п. 1, где антигенсвязывающий домен содержит вариабельную область легкой цепи, содержащую аминокислотную последовательность, включающую SEQ ID NO 7.
3. CAR по п. 1 или 2, где антигенсвязывающий домен содержит вариабельную область тяжелой цепи, содержащую аминокислотную последовательность, включающую SEQ ID NO 8.
4. CAR по п. 1 или 2, где антигенсвязывающий домен содержит аминокислотную последовательность, включающую SEQ ID NO 9.
5. CAR по п. 1 или 2, где антигенсвязывающий домен содержит линкер, включающий SEQ ID NO 11.
6. CAR по п. 1 или 2, дополнительно содержащий лидерную последовательность, включающую SEQ ID NO 10.
7. CAR по п. 1 или 2, где трансмембранный домен содержит i) часть CD8 и/или ii) часть CD28.
8. CAR по п. 1 или 2, где трансмембранный домен содержит аминокислотную последовательность, включающую SEQ ID NO 12 или 18, и/или аминокислотную последовательность, включающую SEQ ID NO 15.
9. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит один или более чем один из i) внутриклеточной части сигналинга CD28, ii) внутриклеточной части сигналинга CD137 и iii) внутриклеточной части сигналинга CD3 дзета.
10. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит аминокислотную последовательность, включающую последовательность SEQ ID NO 16 или 19.
11. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит аминокислотную последовательность, включающую SEQ ID NO 13 или 20.
12. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит аминокислотную последовательность, включающую SEQ ID NO 14, 17 или 21.
13. CAR по п. 1 или 2, где внутриклеточный домен Т-клеточного сигналинга содержит внутриклеточную часть CD28 или содержит внутриклеточную часть сигналинга CD137 и где указанный CAR не содержит внутриклеточный домен сигналинга как CD28, так и CD137.
14. CAR по п. 13, где указанный CAR не содержит внутриклеточный домен сигналинга, полученный от более чем одной костимулирующей Т-клетки молекулы.
15. CAR по п. 1 или 2, содержащий аминокислотную последовательность, включающую любую из SEQ ID NO 22-24.
16. CAR по п. 1 или 2, где внутриклеточный домен сигналинга содержит внутриклеточную часть сигналинга CD 137 и внутриклеточной части сигналинга CD3 дзета.
17. CAR по п. 16, где трансмембранная часть содержит часть CD8.
18. CAR по п. 16, где трансмембранная часть содержит часть CD28.
19. Нуклеиновая кислота, содержащая нуклеотидную последовательность, кодирующую CAR по п. 1 или 2.
20. Нуклеиновая кислота по п. 19, содержащая нуклеотидную последовательность, включающую SEQ ID NO 25.
21. Нуклеиновая кислота по п. 20, дополнительно включающая нуклеотидную последовательность, выбранную из группы, состоящей из SEQ ID NO 26-28.
22. Нуклеиновая кислота по п. 21, включающая нуклеотидную последовательность SEQ ID NO 25 и нуклеотидную последовательность SEQ ID NO 26.
23. Нуклеиновая кислота по п. 21, включающая нуклеотидную последовательность SEQ ID NO 25 и нуклеотидную последовательность SEQ ID NO 27.
24. Рекомбинантный экспрессионный вектор, содержащий нуклеиновую кислоту по п. 19.
25. Выделенная клетка-хозяин, содержащая рекомбинантный экспрессионный вектор по п. 24.
26. Популяция клеток, содержащая по меньшей мере одну клетку-хозяина по п. 25.
27. Фармацевтическая композиция, содержащая CAR по п. 1 или 2 и фармацевтически приемлемый носитель.
28. Способ лечения или профилактики рака у млекопитающего, включающий введение млекопитающему CAR по п. 1 или 2 в количестве эффективном для лечения или профилактики рака у млекопитающего.
29. Способ по п. 28, где рак включает В-клеточную лимфому или В-клеточную лейкемию.
30. Применение клетки-хозяина по п. 25 для изготовления лекарственного средства для обнаружения, лечения или профилактики рака.
31. Применение по п. 30, где рак включает В-клеточную лимфому или В-клеточную лейкемию.
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