肿瘤细胞治疗研究
英文原题：Beyond BCMA: the next wave of CAR T cell therapy in multiple myeloma.
嵌合抗原受体（CAR）T 细胞疗法已改变复发/难治性多发性骨髓瘤的治疗格局。
嵌合抗原受体（CAR）T 细胞疗法改变了复发/难治性多发性骨髓瘤的治疗格局。目前美国食品药品监督管理局（FDA）批准的 CAR T 细胞疗法——伊德卡布他仑赛和西达基奥仑赛——均靶向恶性浆细胞表面的 B 细胞成熟抗原（BCMA）。尽管多数患者初始缓解较深，抗 BCMA CAR T 细胞治疗后复发仍很常见。目前正在研究抗 BCMA CAR T 细胞疗法的获得性耐药。与此同时，研究人员也在探索其他可行抗原靶点，包括 G 蛋白偶联受体 C 类第 5 组 D 成员（GPRC5D）、信号淋巴细胞活化分子家族成员 7（SLAMF7）和 CD38 等。随着这些靶点 CAR T 细胞从临床前研究进入早期临床试验，无论单独使用还是联合抗 BCMA 方案，均显示出很大前景。本综述总结了 BCMA 以外新型 CAR T 细胞靶点的现有数据，这些靶点有望在不久的将来进入治疗领域。
Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment landscape of relapsed/refractory multiple myeloma. The current Food and Drug Administration approved CAR T cell therapies idecabtagene vicleucel and ciltacabtagene autoleucel both target B cell maturation antigen (BCMA), which is expressed on the surface of malignant plasma cells. Despite deep initial responses in most patients, relapse after anti-BCMA CAR T cell therapy is common. Investigations of acquired resistance to anti-BCMA CAR T cell therapy are underway. Meanwhile, other viable antigenic targets are being pursued, including G protein-coupled receptor class C group 5 member D (GPRC5D), signaling lymphocytic activation molecule family member 7 (SLAMF7), and CD38, among others. CAR T cells targeting these antigens, alone or in combination with anti-BCMA approaches, appear to be highly promising as they move from preclinical studies to early phase clinical trials. This review summarizes the current data with novel CAR T cell targets beyond BCMA that have the potential to enter the treatment landscape in the near future.
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