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[多发性骨髓瘤免疫治疗的现状与未来前景]

[Current status and future prospects of immunotherapy for multiple myeloma].

作者信息

Imai Yoichi

机构信息

IMSUT Hospital, The Institute of Medical Science, The University of Tokyo.

出版信息

Rinsho Ketsueki. 2021;62(5):407-417. doi: 10.11406/rinketsu.62.407.

Abstract

The introduction of autologous stem cell transplantation, proteasome inhibitors, and immunomodulatory drugs (IMiDs) has improved the treatment outcome for multiple myeloma (MM). However, many patients develop resistance to existing therapies, and novel treatment strategies for these patients must be established. Therapeutic antibodies including daratumumab targeting CD38 and elotuzumab targeting SLAMF7 have been introduced in the clinic as immunotherapies for MM. These antibodies exert cytotoxic effects on myeloma cells through the activation of effector cells such as natural killer cells and induction of phagocytosis by macrophages. Suppressed anti-tumor immunity may be related to acquisition of drug resistance by myeloma cells in patients with MM. It has been reported that IMiDs such as lenalidomide and pomalidomide enhance the effect of therapeutic antibodies through the stimulation of anti-tumor immunity. This stimulation of anti-tumor immunity is also observed in the effects of anti-CD38 antibodies, such as daratumumab and isatuximab. Therefore, it is expected that combination therapy with anti-CD38 antibodies and IMiDs may enhance anti-tumor immunity. Furthermore, chimeric antigen receptor (CAR) T cell therapy, antibody drug conjugates (ADC), and bispecific antibodies (BsAbs) are in the process of their introduction to the clinic as novel immunotherapies for MM.

摘要

自体干细胞移植、蛋白酶体抑制剂和免疫调节药物(IMiDs)的引入改善了多发性骨髓瘤(MM)的治疗效果。然而,许多患者对现有疗法产生耐药性,因此必须为这些患者制定新的治疗策略。包括靶向CD38的达雷妥尤单抗和靶向信号淋巴细胞激活分子家族成员7(SLAMF7)的埃罗妥珠单抗在内的治疗性抗体已作为MM的免疫疗法引入临床。这些抗体通过激活自然杀伤细胞等效应细胞和诱导巨噬细胞吞噬作用,对骨髓瘤细胞发挥细胞毒性作用。MM患者中抗肿瘤免疫抑制可能与骨髓瘤细胞获得耐药性有关。据报道,来那度胺和泊马度胺等IMiDs通过刺激抗肿瘤免疫增强治疗性抗体的效果。在达雷妥尤单抗和isatuximab等抗CD38抗体的作用中也观察到这种抗肿瘤免疫刺激。因此,预计抗CD38抗体与IMiDs联合治疗可能增强抗肿瘤免疫。此外,嵌合抗原受体(CAR)T细胞疗法、抗体药物偶联物(ADC)和双特异性抗体(BsAb)正在作为MM的新型免疫疗法引入临床。

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