CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy.
Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy.
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CAR-T 细胞疗法为多发性骨髓瘤(MM)治疗开辟了新时代。众多临床研究,尤其是靶向B细胞成熟抗原(BCMA)的CAR-T 研究,显示其治疗复发/难治性多发性骨髓瘤(R/R MM)疗效显著。然而,相当一部分患者在BCMA CAR-T 治疗后仍会复发或进展,这归因于多种因素,包括抗原逃逸、CAR-T 制备因素、T细胞耗竭、肿瘤微环境抑制作用以及既往治疗的影响。CAR-T 治疗后复发时有效治疗选择稀少,且缺乏成熟的挽救治疗方案,使复发患者预后不佳。近年来,一些学术机构通过再次输注BCMA CAR-T、转换为非BCMA靶向CAR-T、双靶点CAR-T、双特异性抗体或其他新型疗法,开展BCMA CAR-T 治疗后复发患者的挽救治疗并取得一定成效。本综述总结BCMA CAR-T 治疗后耐药或复发的机制及当前挽救治疗的现有数据,以期为优化临床挽救治疗提供思路。
Chimeric antigen receptor T-cell (CAR-T) therapy has ushered in a new era for the treatment of multiple myeloma (MM). Numerous clinical studies, especially those involving B-cell maturation antigen (BCMA)-directed CAR-T, have shown remarkable efficacy in patients with relapsed or refractory multiple myeloma (R/R MM).
However, a considerable number of patients still experience disease recurrence or progression after BCMA CAR-T treatment, which is attributed to various factors, including antigen escape, CAR-T manufacturing factors, T cell exhaustion, inhibitory effects of tumor microenvironment and impact of prior treatments. The scarcity of effective treatment options following post-CAR-T disease recurrence, coupled with the lack of well-established salvage regimens, leaves patients who do relapse facing a bleak prognosis.
In recent years, some academic institutions have achieved certain results in salvage treatments of patients with relapse after BCMA CAR-T treatment through secondary infusion of BCMA CAR-T, changing to non-BCMA-directed CAR-T, double-target CAR-T, bispecific antibodies or other novel therapies. This review summarizes the mechanisms of resistance or relapse after BCMA CAR-T administration and the available data on current salvage treatments, hoping to provide ideas for optimizing clinical salvage therapies.
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