How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma.
How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma.
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DOI：
10.1158/1078-0432.ccr-19-2111
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发表时间：
2020-04-01
期刊：
影响因子：
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通讯作者：
Dhodapkar MV
中科院分区：
文献类型：
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作者：
Cohen AD;Raje N;Fowler JA;Mezzi K;Scott EC;Dhodapkar MV
多发性骨髓瘤（MM）是一种以浆细胞生长不受调节为特征的血液恶性肿瘤，其进展与先天性和适应性免疫系统功能障碍的增加相关，特别是在T细胞库中。虽然MM的治疗进展已导致更深和更持久的临床反应，但该疾病对大多数患者来说仍然无法治愈。旨在克服免疫抑制性肿瘤微环境和激活宿主免疫系统的治疗策略最近在MM中显示出希望，特别是在复发性和/或难治性疾病环境中。由于T细胞依赖性免疫肿瘤学疗法的功效可能受内源性T细胞库的健康影响，因此这些疗法也可以在替代治疗环境（例如，前体疾病;干细胞移植后）。这篇综述描述了MM演变过程中T细胞相关的变化，并概述了正在研究的T细胞依赖性免疫肿瘤学方法。正在探索MM疾病连续体中的疫苗和检查点抑制剂干预;迄今为止，已在复发性和/或难治性疾病环境中主要评价了重定向患者T细胞以引发抗MM应答的治疗方式，即嵌合抗原受体（CAR）T细胞和双特异性抗体（包括BiTE® [双特异性T细胞受体]分子）。针对B细胞成熟抗原（BCMA）的CAR T细胞和双特异性抗体/抗体构建体已经产生了令人兴奋的结果，临床数据显示了深度反应。增加对免疫系统和MM在整个病程中复杂相互作用的理解将有助于最大限度地发挥MM中T细胞依赖性免疫肿瘤学策略的潜力。
The progression of multiple myeloma (MM), a hematologic malignancy characterized by unregulated plasma cell growth, is associated with increasing innate and adaptive immune system dysfunction, notably in the T-cell repertoire. Although treatment advances in MM have led to deeper and more durable clinical responses, the disease remains incurable for most patients. Therapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and activating the host immune system have recently shown promise in MM, particularly in the relapsed and/or refractory disease setting. As the efficacy of T-cell–dependent immuno-oncology therapy is likely affected by the health of the endogenous T-cell repertoire, these therapies may also provide benefit in alternate treatment settings (e.g., precursor disease; after stem cell transplantation). This review describes T-cell–associated changes during the evolution of MM and provides an overview of T-cell–dependent immuno-oncology approaches under investigation. Vaccine and checkpoint inhibitor interventions are being explored across the MM disease continuum; treatment modalities that redirect patient T cells to elicit an anti-MM response, namely chimeric antigen receptor (CAR) T cells and bispecific antibodies (including BiTE® [bispecific T-cell engager] molecules), have been primarily evaluated to date in the relapsed and/or refractory disease setting. CAR T cells and bispecific antibodies/antibody constructs directed against B-cell maturation antigen (BCMA) have generated excitement, with clinical data demonstrating deep responses. An increased understanding of the complex interplay between the immune system and MM throughout the disease course will aid in maximizing the potential for T-cell–dependent immuno-oncology strategies in MM.