嵌合抗原受体 (CAR) T 细胞疗法在多发性骨髓瘤中的应用前景。
The promise of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma.
机构信息
Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA.
Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Cell Immunol. 2019 Nov;345:103964. doi: 10.1016/j.cellimm.2019.103964. Epub 2019 Aug 13.
A cure for multiple myeloma (MM), a malignancy of plasma cells, remains elusive. Nearly all myeloma patients will eventually relapse and develop resistance to currently available treatments. There is an unmet medical need to develop novel and effective therapies that can induce sustained responses. Early phase clinical trials using chimeric antigen receptor (CAR) T cell therapy have shown great promise in the treatment of relapsed and/or refractory MM. In this review article, we provide an overview of the CAR constructs, the gene transfer vector systems, and approaches for T cell activation and expansion. We then summarize the outcomes of several early phase clinical trials of CAR T cell therapy in MM and the novel CAR T targets that are under development. Finally, we explore the potential mechanisms that result in disease relapse after CAR T therapy and propose future directions in CAR T therapy in MM.
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，目前仍无法治愈。几乎所有的骨髓瘤患者最终都会复发，并对现有治疗产生耐药性。因此，开发新型、有效的治疗方法，诱导持久缓解是目前尚未满足的医学需求。嵌合抗原受体（CAR）T 细胞疗法的早期临床试验在治疗复发和/或难治性 MM 方面显示出巨大的潜力。在这篇综述文章中，我们概述了 CAR 结构、基因转导载体系统以及 T 细胞激活和扩增的方法。然后，我们总结了 CAR T 细胞治疗 MM 的几项早期临床试验的结果和正在开发的新型 CAR T 靶点。最后，我们探讨了 CAR T 治疗后疾病复发的潜在机制，并提出了 MM 中 CAR T 治疗的未来方向。
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