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基于T细胞的多发性骨髓瘤细胞免疫疗法:当前进展

T-Cell-Based Cellular Immunotherapy of Multiple Myeloma: Current Developments.

作者信息

Simmons Gary L, Castaneda Puglianini Omar

机构信息

Cellular Immunotherapies and Transplant Program, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

Department of Blood & Marrow Transplantation & Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

出版信息

Cancers (Basel). 2022 Aug 31;14(17):4249. doi: 10.3390/cancers14174249.

Abstract

T-cell-based cellular therapy was first approved in lymphoid malignancies (B-cell acute lymphoblastic leukemia and large B-cell lymphoma) and expanding its investigation and application both in hematological and non-hematological malignancies. Two anti-BCMA (B cell maturation antigen) CAR (Chimeric Antigen Receptor) T-cell therapies have been recently approved for relapsed and refractory multiple myeloma with excellent efficacy even in the heavily pre-treated patient population. This new therapeutic approach significantly changes our practice; however, there is still room for further investigation to optimize antigen receptor engineering, cell harvest/selection, treatment sequence, etc. They are also associated with unique adverse events, especially CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome), which are not seen with other anti-myeloma therapies and require expertise for management and prevention. Other T-cell based therapies such as TCR (T Cell Receptor) engineered T-cells and non-genetically engineered adoptive T-cell transfers (Vγ9 Vδ2 T-cells and Marrow infiltrating lymphocytes) are also actively studied and worth attention. They can potentially overcome therapeutic challenges after the failure of CAR T-cell therapy through different mechanisms of action. This review aims to provide readers clinical data of T-cell-based therapies for multiple myeloma, management of unique toxicities and ongoing investigation in both clinical and pre-clinical settings.

摘要

基于T细胞的细胞疗法最初被批准用于淋巴系统恶性肿瘤(B细胞急性淋巴细胞白血病和大B细胞淋巴瘤),并且其在血液系统恶性肿瘤和非血液系统恶性肿瘤中的研究与应用正在不断扩展。两种抗BCMA(B细胞成熟抗原)嵌合抗原受体(CAR)T细胞疗法最近已被批准用于复发难治性多发性骨髓瘤,即使在预处理程度很高的患者群体中也具有出色的疗效。这种新的治疗方法显著改变了我们的治疗实践;然而,在优化抗原受体工程、细胞采集/选择、治疗顺序等方面仍有进一步研究的空间。它们还与独特的不良事件相关,尤其是细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS),这些在其他抗骨髓瘤疗法中未见,需要专业知识进行管理和预防。其他基于T细胞的疗法,如工程化T细胞受体(TCR)T细胞和非基因工程的过继性T细胞转移(Vγ9Vδ2T细胞和骨髓浸润淋巴细胞)也在积极研究中,值得关注。它们有可能通过不同的作用机制克服CAR T细胞疗法失败后的治疗挑战。本综述旨在为读者提供基于T细胞的多发性骨髓瘤治疗的临床数据、独特毒性的管理以及临床和临床前环境中的 ongoing investigation。 (注:最后“ongoing investigation”未准确对应的中文表述,可根据上下文理解为“正在进行的研究”之类意思)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d783/9455067/9c19741959ab/cancers-14-04249-g001.jpg

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