肿瘤细胞治疗研究
英文原题：Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial.
我们的研究表明，双特异性 BC19 CAR T 细胞治疗 R/R MM 患者可行、安全且有效。
尽管靶向 B 细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T 细胞疗法在复发/难治性多发性骨髓瘤（R/R MM）中取得较高应答率，单靶点免疫治疗仍会出现原发耐药和复发。本研究设计了靶向 BCMA/CD19 的双特异性 BC19 CAR-T 细胞，并在体外和体内评估其抗骨髓瘤活性。临床前结果显示，BC19 CAR 可特异识别靶抗原，BC19 CAR-T 细胞可选择性杀伤 BCMA 或 CD19 阳性肿瘤细胞，并在异种移植小鼠模型中表现出强效、抗原特异性的抗肿瘤活性。研究进一步开展开放标签、单臂 I/II 期试验，纳入 50 例 R/R MM 患者（ChiCTR2000033567），主要终点为安全性。BC19 CAR-T 耐受性良好；3 级及以上细胞因子释放综合征发生率为 8%，1 级神经毒性事件发生率为 4%，达到预设主要终点。次要终点包括：总缓解率 92%，中位无进展生存期 19.7 个月，中位总生存期 19.7 个月，中位缓解持续时间尚未达到。研究表明，双特异性 BC19 CAR-T 用于 R/R MM 患者具有可行性、安全性和疗效。
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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