多发性骨髓瘤
CD19
耐火材料(行星科学)
医学
汽车T细胞治疗
嵌合抗原受体
肿瘤科
癌症研究
免疫学
T细胞
生物
抗体
免疫系统
天体生物学
作者
Ming Shi,Jiaojiao Wang,Hongming Huang,D Liu,Hai Cheng,Wei Xu,Wei Chen,Zhiling Yan,Wei Sang,Kunming Qi,Depeng Li,Feng Zhu,Zhenyu Li,Jianlin Qiao,Q Wu,Lingyu Zeng,Xiaoming Fei,Weiying Gu,Yulun Miao,Kailin Xu,Junnian Zheng,Jiang Cao
标识
DOI:10.1038/s41467-024-47801-8
摘要
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.
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