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RU2019132475A - Т-клетки, модифицированные химерным рецептором антигена, нацеленным на cs1, для лечения амилоидоза al - Google Patents

Т-клетки, модифицированные химерным рецептором антигена, нацеленным на cs1, для лечения амилоидоза al Download PDF

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RU2019132475A
RU2019132475A RU2019132475A RU2019132475A RU2019132475A RU 2019132475 A RU2019132475 A RU 2019132475A RU 2019132475 A RU2019132475 A RU 2019132475A RU 2019132475 A RU2019132475 A RU 2019132475A RU 2019132475 A RU2019132475 A RU 2019132475A
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amino acid
chimeric antigen
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Сюли ВАН
Стивен Дж. ФОРМЭН
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Сити Оф Хоуп
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Claims (14)

1. Способ лечения амилоидоза легкой цепи, включающий введение пациенту, нуждающемуся в этом, популяции человеческих Т-клеток, трансдуцированных вектором, содержащим кассету экспрессии, кодирующую химерный рецептор антигена, где химерный рецептор антигена содержит: scFv против CS1; спейсерную область; трансмембранный домен; домен косигнализации и домен сигнализации CD3ζ.
2. Способ по п. 1, в котором химерный рецептор антигена содержит: scFv против CS1; спейсерную область; трансмембранный домен CD28; домен косигнализации CD28 и домен сигнализации CD3ζ.
3. Способ по п. 1, в котором химерный рецептор антигена содержит: scFv против CS1; спейсерную область; трансмембранный домен CD4; домен косигнализации 4-1 ВВ и домен сигнализации CD3ζ.
4. Способ по п. 1, в котором химерный рецептор антигена содержит: scFv против CS1; спейсерную область, содержащую аминокислотную последовательность, выбранную из SEQ ID NO: 2-5 и 9-12; трансмембранный домен CD4; домен косигнализации 4-1 ВВ и домен сигнализации CD3ζ.
5. Способ по п. 1, в котором химерный рецептор антигена содержит: scFv против CS1; спейсерную область, содержащую аминокислотную последовательность, выбранную из SEQ ID NO: 2-5 и 9-12; трансмембранный домен CD28; домен косигнализации CD28 и домен сигнализации CD3ζ.
6. Способ по п. 1, в котором химерный рецептор антигена содержит: scFv против CS1; спейсерную область, содержащую аминокислотную последовательность, выбранную из SEQ ID NO: 2-5 и 9-12; трансмембранный домен CD4; домен косигнализации 4-1 ВВ и домен сигнализации CD3ζ.
7. Способ по п. 1, в котором химерный рецептор антигена содержит: спейсерную область, содержащую аминокислотную последовательность, выбранную из SEQ ID NO: 2-5 и 9-12; трансмембранный домен CD28; домен косигнализации CD28 и домен сигнализации CD3ζ.
8. Способ по п. 1, в котором химерный рецептор антигена содержит аминокислотную последовательность, по меньшей мере на 95% идентичную аминокислотной последовательности, выбранной из SEQ ID NO: 30, 31, 33, 34, 36, 37, 39, 40, 42, 43, 44 и 45.
9. Способ по п. 1, в котором химерный рецептор антигена содержит аминокислотную последовательность, идентичную аминокислотной последовательности, выбранной из SEQ ID NO: 30, 31, 33, 34, 36, 37, 39, 40, 42, 43, 44 и 45.
10. Способ по п. 1, в котором химерный рецептор антигена содержит аминокислотную последовательность, идентичную аминокислотной последовательности, выбранной из SEQ ID NO: 30, 31, 33, 34, 36, 37, 39, 40, 42, 43, 44 и 45, причем каждая имеет не более 5 замен одиночных аминокислот.
11. Способ по п. 1, в котором по меньшей мере 20%, 30% или 40% трансдуцированных человеческих Т-клеток представляют собой центральные Т-клетки памяти.
12. Способ по п. 1, в котором по меньшей мере 30% трансдуцированных человеческих Т-клеток представляют собой CD4+ и CD62L+ или CD8+ и CD62L+.
13. Способ по п. 1, в котором популяция человеческих Т-клеток является аутологичной по отношению к данному пациенту.
14. Способ по п. 1, в котором популяция человеческих Т-клеток является аллогенной по отношению к данному пациенту.
RU2019132475A 2017-03-20 2018-03-20 Т-клетки, модифицированные химерным рецептором антигена, нацеленным на cs1, для лечения амилоидоза al RU2774895C2 (ru)

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US201762473980P 2017-03-20 2017-03-20
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PCT/US2018/023381 WO2018175453A1 (en) 2017-03-20 2018-03-20 Cs1 targeted chimeric antigen receptor-modified t cells for treatment of al amyloidosis

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