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Immunotherapy of multiple myeloma.
The Journal of Clinical Investigation ( IF 13.3 ) Pub Date : 2020-03-09 , DOI: 10.1172/jci129205
Simone A Minnie 1 , Geoffrey R Hill 1, 2
Affiliation  

Multiple myeloma (MM), a bone marrow–resident hematological malignancy of plasma cells, has remained largely incurable despite dramatic improvements in patient outcomes in the era of myeloma-targeted and immunomodulatory agents. It has recently become clear that T cells from MM patients are able to recognize and eliminate myeloma, although this is subverted in the majority of patients who eventually succumb to progressive disease. T cell exhaustion and a suppressive bone marrow microenvironment have been implicated in disease progression, and once these are established, immunotherapy appears largely ineffective. Autologous stem cell transplantation (ASCT) is a standard of care in eligible patients and results in immune effects beyond cytoreduction, including lymphodepletion, T cell priming via immunogenic cell death, and inflammation; all occur within the context of a disrupted bone marrow microenvironment. Recent studies suggest that ASCT reestablishes immune equilibrium and thus represents a logical platform in which to intervene to prevent immune escape. New immunotherapies based on checkpoint inhibition targeting the immune receptor TIGIT and the deletion of suppressive myeloid populations appear attractive, particularly after ASCT. Finally, the immunologically favorable environment created after ASCT may also represent an opportunity for approaches utilizing bispecific antibodies or chimeric antigen receptor T cells.



中文翻译:


多发性骨髓瘤的免疫治疗。



多发性骨髓瘤(MM)是一种骨髓内浆细胞恶性血液病,尽管在骨髓瘤靶向药物和免疫调节剂时代患者的治疗效果有了显着改善,但它在很大程度上仍然无法治愈。最近已经明确,多发性骨髓瘤患者的 T 细胞能够识别并消除骨髓瘤,尽管这一点在大多数最终死于进展性疾病的患者中被破坏了。 T 细胞耗竭和抑制性骨髓微环境与疾病进展有关,一旦这些因素确定,免疫疗法似乎基本上无效。自体干细胞移植 (ASCT) 是符合条件的患者的一种护理标准,除了细胞减灭之外还能产生免疫效应,包括淋巴细胞清除、通过免疫原性细胞死亡启动 T 细胞和炎症;所有这些都发生在骨髓微环境被破坏的背景下。最近的研究表明,ASCT 重建了免疫平衡,因此代表了一个干预以防止免疫逃逸的逻辑平台。基于针对免疫受体 TIGIT 的检查点抑制和抑制性骨髓细胞群删除​​的新免疫疗法似乎很有吸引力,特别是在 ASCT 后。最后,ASCT 后创造的免疫有利环境也可能为利用双特异性抗体或嵌合抗原受体 T 细胞的方法提供机会。

更新日期:2020-04-03
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