Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), German Cancer Consortium (DKTK), Heidelberg, Germany.
Int J Cancer. 2020 Oct 15;147(8):2029-2041. doi: 10.1002/ijc.33002. Epub 2020 Apr 30.
Despite major advances in the treatment of multiple myeloma (MM), it remains a largely incurable disease with long-term control often dependent on continuous therapy. More effective, better tolerated treatments are therefore required to achieve durable remissions and to improve the quality of life of MM patients. Adoptive immunotherapy employing T cells expressing chimeric antigen receptors (CAR) is currently among the most promising treatment approaches in cancer. Within the target portfolio for MM immunotherapy, B-cell maturation antigen (BCMA) is among the most widely studied target antigens. BCMA is consistently expressed on MM cells and, importantly, is not expressed in critical healthy tissue. For this reason, it is an ideal target for MM immunotherapy. Several clinical trials evaluating different BCMA-targeting CAR constructs have been initiated and early results are very promising. However, in this rapidly developing clinical landscape, the ultimate role of BCMA-specific CAR-T cell therapy remains unclear. In this review, we will summarize currently available clinical data on BCMA-directed CAR-T cells and discuss potential future perspective for this promising treatment approach in MM.
尽管多发性骨髓瘤(MM)的治疗取得了重大进展,但它仍然是一种基本上无法治愈的疾病,长期控制通常依赖于持续治疗。因此,需要更有效、更耐受的治疗方法来实现持久缓解并改善 MM 患者的生活质量。嵌合抗原受体(CAR)表达 T 细胞的过继免疫疗法是癌症治疗中最有前途的方法之一。在 MM 免疫治疗的目标组合中,B 细胞成熟抗原(BCMA)是研究最广泛的靶标抗原之一。BCMA 在 MM 细胞上持续表达,重要的是,它不在关键的健康组织中表达。因此,它是 MM 免疫治疗的理想靶标。已经启动了几项评估不同 BCMA 靶向 CAR 构建体的临床试验,早期结果非常有希望。然而,在这个快速发展的临床领域,BCMA 特异性 CAR-T 细胞治疗的最终作用尚不清楚。在这篇综述中,我们将总结目前关于 BCMA 定向 CAR-T 细胞的临床数据,并讨论这种有前途的治疗方法在 MM 中的潜在未来前景。