Ding Lijuan, Hu Yongxian, Huang He
Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Institute of Hematology, Zhejiang University, Hangzhou, China.
Stem Cell Investig. 2021 Jan 15;8:1. doi: 10.21037/sci-2020-029. eCollection 2021.
Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, which leads to suppressed hematopoietic and osteolytic diseases. Despite the use of traditional chemotherapy, hematopoietic stem cell transplantation (HSCT) and targeted drugs, MM still cannot be completely cured. In recent years, chimeric antigen receptor (CAR) T cells have revolutionized immunotherapy and cancer treatment. The great success of CAR-T cells in leukemia and lymphoma has promoted its development in MM. The primary requisite for developing clinically effective CAR-T cells suitable for MM is to identify the appropriate targets. In early clinical trials, CAR-T cells targeting B-cell maturation antigen (BCMA) have shown significant anti-MM activity. Currently popular targets in clinical research and preclinical research include CD138, CD38, CS1, CD19, κ light chain, CD56, CD44v6, Lewis Y, NY-ESO-1, CD229, etc. Common toxicities such as cytokine release syndrome (CRS) and neurotoxicity also occur but controllable. MM cells are mainly localized in bone marrow, therefore, the bone marrow microenvironment has a significant effect on the therapeutic effect of CAR-T cells. Targeting both MM cells and the bone marrow microenvironment is currently the most promising treatment. In this review, we provide a comprehensive overview of CAR-T cell therapy in MM, as well as outline potential targets and methods that can overcome local immunosuppression and improve the efficacy of CAR-T cells.
多发性骨髓瘤（MM）是一种浆细胞恶性增殖性疾病，可导致造血功能受抑制和溶骨性疾病。尽管使用了传统化疗、造血干细胞移植（HSCT）和靶向药物，但MM仍无法完全治愈。近年来，嵌合抗原受体（CAR）T细胞彻底改变了免疫疗法和癌症治疗。CAR-T细胞在白血病和淋巴瘤治疗中的巨大成功推动了其在MM治疗中的发展。开发适用于MM的临床有效CAR-T细胞的首要条件是确定合适的靶点。在早期临床试验中，靶向B细胞成熟抗原（BCMA）的CAR-T细胞已显示出显著的抗MM活性。目前临床研究和临床前研究中常用的靶点包括CD138、CD38、CS1、CD19、κ轻链、CD56、CD44v6、Lewis Y、NY-ESO-1、CD229等。常见的毒性反应如细胞因子释放综合征（CRS）和神经毒性也会出现，但可控。MM细胞主要定位于骨髓，因此，骨髓微环境对CAR-T细胞的治疗效果有显著影响。同时靶向MM细胞和骨髓微环境是目前最有前景的治疗方法。在本综述中，我们全面概述了MM的CAR-T细胞疗法，并概述了可克服局部免疫抑制并提高CAR-T细胞疗效的潜在靶点和方法。
