Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland.
St. John's Cancer Centre, 20-090 Lublin, Poland.
Cells. 2020 Apr 16;9(4):983. doi: 10.3390/cells9040983.
Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit-risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen.
尽管现代抗癌疗法取得了重大进展,但多发性骨髓瘤(MM)对大多数患者来说仍然无法治愈。经过近三十年的发展,嵌合抗原受体(CAR)T 细胞疗法现在有机会彻底改变治疗格局,满足未满足的临床需求。然而,仍有几个主要障碍需要克服。在这里,我们讨论了 CAR T 细胞疗法治疗 MM 的最新进展,重点介绍了未来的方向和可能存在的风险。目前,CAR T 细胞疗法治疗 MM 处于临床研究的第一阶段,大多数研究都集中在针对 B 细胞成熟抗原(BCMA)的 CAR T 细胞上,但也在评估其他抗原,如分化群 138(CD138,syndecan-1)。尽管这种疗法与细胞因子释放综合征和神经毒性等副作用有关,并且已经观察到复发,但获益风险平衡和巨大的潜力推动了正在进行的临床进展。为了实现最近临床试验成功的承诺并最大限度地发挥 CAR T 的潜力,未来的努力应集中在减少副作用、新型靶向抗原、不同类型的 CAR T 的联合使用以及开发针对多种抗原的 CAR T 细胞上。