肿瘤细胞治疗研究
英文原题：Cellular therapy for multiple myeloma: what's now and what's next.
尽管多发性骨髓瘤（MM）的治疗取得了显著改善，治愈仍难以实现，而蛋白酶体抑制剂、免疫调节药物和抗 CD38 单克隆抗体治疗失败的患者由于缺乏标准治疗仍是一大难题。
尽管多发性骨髓瘤（MM）治疗取得显著进展，治愈仍难以实现。对蛋白酶体抑制剂、免疫调节药物和抗CD38单克隆抗体均耐药的患者，由于缺乏标准治疗且生存率极低，仍是治疗难题。T细胞重定向疗法，包括双特异性T细胞衔接器和嵌合抗原受体（CAR）T细胞，已改变经三类药物治疗后复发/难治性MM（RRMM）患者的治疗结局。B细胞成熟抗原（BCMA）已被证实是MM的重要靶点；靶向BCMA的CAR T细胞在晚期RRMM人群中显示出前所未有的疗效，且缓解持续时间较长，已有两种BCMA CAR T细胞产品获批。然而，与CD19靶向CAR领域的既往经验不同，目前生存曲线尚未出现平台期，疾病仍会复发。因此，仍需进一步提高疗效。更早在疾病病程中应用这类疗法，以及开发新一代CAR，可能进一步增强疗效。本文综述目前已获批、用于RRMM的先进BCMA靶向CAR T细胞疗法，并讨论以优化患者照护和创新CAR设计为重点的未来进展。
Despite significant improvement in the treatment of multiple myeloma (MM), a cure remains elusive, and patients failing proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies remain a challenge due to a lack of standard of care treatment and a dismal survival rate. The development of T-cell redirecting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T cells, have transformed the outcome of triple-class exposed relapsed and refractory MM (RRMM). B-cell maturation antigen (BCMA) has proven to be an important target in MM, and BCMA-directed CAR T cells have shown unprecedented efficacy with a prolonged duration of response in a population with advanced RRMM, leading to the approval of 2 different BCMA CAR T-cell products. Still, and in contrast to prior experience in the field of CD19-directed CARs, no plateau has been seen in the survival curves, and relapses continue to occur. Therefore, further improvement is needed. Early use in the course of the disease as well as of next- generation CARs may further augment the efficacy of these therapies. In this review we address current state-of-the-art approved BCMA-directed CAR T-cell therapy in RRMM, as well as potential future developments focused on optimizing patient care and novel CAR designs.
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