TRBC1+ T 细胞耗竭可增强抗 TRBC1 CAR-T 治疗 T 细胞恶性肿瘤的疗效。
Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies.
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Key Laboratory of Carcinogenesis and Translational Research, Departments of Lymphoma, Radiology and Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
出版信息
Mol Cancer. 2020 Nov 21;19(1):162. doi: 10.1186/s12943-020-01282-7.
Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing.
靶向 T 细胞受体 β 链恒定区 1（TRBC1）嵌合抗原受体 T 细胞（CAR-T）可以特异性杀伤 TRBC1+T 细胞恶性肿瘤。然而，在转导 TRBC1+T 细胞的抗 TRBC1 CAR 上过度表达的 CAR（CAR-C1）与自身的 TRBC1 结合，从而使其他抗 TRBC1 CAR-T 无法识别 TRBC1，此外，只有剩余未占据的 CAR 能够识别 TRBC1+细胞，这极大地降低了 CAR-C1 的治疗效力。此外，抗 TRBC1 CAR-T 和 TRBC1+细胞的共培养可以促进 CAR-T 的耗竭和终末分化。这些发现为在制造抗 TRBC1 CAR-T 之前预先消耗 TRBC1+T 细胞提供了依据。
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