Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial

Autor: Ming Shi, Jiaojiao Wang, Hongming Huang, Dan Liu, Hai Cheng, Xu Wang, Wei Chen, Zhiling Yan, Wei Sang, Kunming Qi, Depeng Li, Feng Zhu, Zhenyu Li, Jianlin Qiao, Qingyun Wu, Lingyu Zeng, Xiaoming Fei, Weiying Gu, Yuqing Miao, Kailin Xu, Junnian Zheng, Jiang Cao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 2041-1723
79117392
DOI: 10.1038/s41467-024-47801-8
Popis: Abstract Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.
Databáze: Directory of Open Access Journals
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