RU2018107535A - Химерный антигенный рецептор и т-клетки, в которых экспрессируется химерный антигенный рецептор - Google Patents
Химерный антигенный рецептор и т-клетки, в которых экспрессируется химерный антигенный рецептор Download PDFInfo
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- RU2018107535A RU2018107535A RU2018107535A RU2018107535A RU2018107535A RU 2018107535 A RU2018107535 A RU 2018107535A RU 2018107535 A RU2018107535 A RU 2018107535A RU 2018107535 A RU2018107535 A RU 2018107535A RU 2018107535 A RU2018107535 A RU 2018107535A
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Claims (22)
1. Химерный антигенный рецептор, содержащий антигенсвязывающий домен; шарнирную область; трансмембранный домен; костимулирующий домен; и цитоплазматический домен сигнализации, отличающийся тем, что костимулирующий домен представляет собой мутированный CD28 или TNFRSF9.
2. Химерный антигенный рецептор по п.1, отличающийся тем, что в мутированном CD28, аминокислота в 6-ом - 9-ом положениях аминокислотной последовательности, обозначенной как Последовательность № 7, заменена из RLLH на RGGH или аминокислоту, имеющей сходное свойство с RGGH.
3. Химерный антигенный рецептор по п.2, отличающийся тем, что в случае аминокислоты, имеющей сходное свойство с RGGH, глицин (G) заменен на аланин(A), валин(V), лейцин(L) или изолейцин(I).
4. Химерный антигенный рецептор по любому из пп. 1-3, отличающийся тем, что костимулирующий домен состоит из мутированного CD28 и TNFRSF9.
5. Химерный антигенный рецептор, содержащий антигенсвязывающий домен; шарнирную область; трансмембранный домен; костимулирующий домен; и цитоплазматический домен сигнализации, отличающийся тем, что три глицина или аминокислоты, имеющих сходное свойство с глицином, дополнительно вводят между антигенсвязывающим доменом и шарнирной областью.
6. Химерный антигенный рецептор по п.5, отличающийся тем, что аминокислота, имеющая сходное свойство с глицином, представляет собой аланин(A), валин(V), лейцин(L) или изолейцин(I).
7. Химерный антигенный рецептор, содержащий антигенсвязывающий домен; шарнирную область; трансмембранный домен; костимулирующий домен; и цитоплазматический домен сигнализации, отличающийся тем, что антигенсвязывающий домен связыватся с антигеном, выбранным из группы, состоящей из IL13Rα2, антигена, ассоциированного с ангиогенной активностью, EGFRvIII, EphA2, αVβ3, и глипикана 1.
8 Химерный антигенный рецептор по п.7, отличающийся тем, что антигенсвязывающий домен связывается с IL13Rα2.
9. Химерный антигенн рецептор по п.8, отличающийся тем, что антигенсвязывающий домен имеет аминокислотную последовательность, где 11-е положение аминокислотной последовательности, обозначенной как Последовательность № 1, заменено на лизин, и 107-е положение представляет собой замененный лизин.
10. Химерный антигенный рецептор по п.8, отличающийся тем, что в антигенсвязывающем домене, 11-ое, 64-ое, 67-ое и 107-ое положения аминокислотной последовательности, обозначенной как Последовательность № 1, являются замещенными лизином(K), аспарагиновой кислотой(D), аспарагиновой кислотой(D) и лизином(K), или аминокислотой, сходной с ними.
11. Химерный антигенный рецептор по п.10, отличающийся тем, что аминокислота, замененная на аминокислоту, сходную с ней, заменена на аргинин (R) или гистидин (H), вместо лизина (K), в 11-ом положении; на глутаминовую кислоту (E), вместо аспарагиновой кислоты (D), в 64-ом и 67-ом положениях; и гистидин (H), вместо лизина (K), в 107-ом положении.
12. Химерный антигенный рецептор, содержащий антигенсвязывающий домен; шарнирную область; трансмембранный домен; костимулирующий домен; и цитоплазматический домен сигнализации, отличающийся тем, что в цитоплазматическом домене сигнализации используют домен сигнализации CD3ζ нормального пациента, где содержится избыточный глутамин.
13. Химерный антигенный рецептор по п.12, отличающийся тем, что избыточный глутамин является глутамином, присутствующем в 50-ом положении домена сигнализации CD3ζ нормального пациента.
14. Химерный антигенный рецептор по п.13, отличающийся тем, что домен сигнализации CD3ζ имеет последовательность, обозначенную как Последовательность № 13.
15. Химерный антигенный рецептор по п.1, обозначенный как Последовательность № 14.
16. Химерный антигенный рецептор по п.1, обозначенный как Последовательность № 15.
17. CAR-T-клетка, в которой экспрессируется химерный антигенный рецептор по любому одному из пп. 1, 5, 7, 10, 12 или 16.
18. Химерный антигенный рецептор по п.7, связывающийся с антигеном, ассоциированным с ангиогенной активностью, обозначенным как Последовательность № 17 или Последовательность № 18.
19. Химерный антигенный рецептор по п.7, связывающийся с EGFRvIII, обозначенным как Последовательность № 19 или Последовательность № 20.
20. Химерный антигенный рецептор по п.7, связывающийся с EphA2, обозначенным как Последовательность № 21 или Последовательность № 22.
21. Химерный антигенный рецептор по п.7, связывающийся с αVβ3, обозначенным как Последовательность № 23 или Последовательность № 24.
22. Химерный антигенный рецептор по п.7, связывающийся с глипиканом 1, обозначенным как Последовательность № 25 или Последовательность № 26.
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WO2021168000A1 (en) * | 2020-02-17 | 2021-08-26 | University Of Virginia Patent Foundation | CAR T CELLS TARGETING THE INTEGRIN ALPHAv BETA3 EXHIBIT ROBUST ANTI-TUMOR RESPONSES AGAINST GLIOMAS AND OTHER SOLID TUMOR MALIGNANCIES |
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