BCMA CAR-T细胞治疗的耐药机制及优化策略研究

嵌合抗原受体T细胞（chimeric antigen receptor T cells，CAR-T）疗法在血液系统肿瘤治疗中已展示出卓越成效。BCMA抗原在骨髓瘤细胞表面普遍表达，是合适高效的CAR-T治疗靶抗原。尤其是对于复发/难治性多发性骨髓瘤患者，BCMA CAR-T细胞治疗缓解率高，多数患者在输注1年后仍可在体内检测到CAR-T细胞。但是耐药与疾病复发仍是目前临床管理中面对的关键问题。本文将从多发性骨髓瘤细胞免疫逃逸、CAR-T产品因素、既往治疗方案及肿瘤免疫微环境的抑制等几个方面来探讨BCMA CAR-T细胞疗法的应答响应因素及耐药诱导机制，并提出可能的优化策略，以期为未来探索提供参考意义。

How I treat relapsed multiple myeloma

Chimeric antigen receptor T cell (CAR-T) therapy has produced remarkable results in the treatment of hematological tumors. The BCMA antigen is widely expressed on the surface of multiple myeloma cells and is a suitable, efficient target for CAR-T therapy. BCMA CAR-T cell therapy has a high response rate for relapsed or refractory patients in particular, and CAR-T cells are still detectable in most patients 1 year after infusion. However, drug resistance and disease recurrence remain key problems in clinical management. In this paper, we discuss the response factors and resistance induction mechanism of BCMA CAR-T cell therapy from several perspectives, such as the immune escape of multiple myeloma cells, CAR-T product factors, previous treatment regimens, and tumor immune microenvironment inhibition. We also propose possible optimization strategies in order to provide reference for future exploration.