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过继性细胞免疫疗法的进展及多发性骨髓瘤的治疗突破。

Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma.

作者信息

Pu Jingjing, Liu Ting, Sharma Amit, Jiang Liping, Wei Feng, Ren Xiubao, Schmidt-Wolf Ingo G H, Hou Jian

机构信息

Department of Integrated Oncology, Center for Integrated Oncology (CIO) Bonn, University Hospital Bonn, 53127, Bonn, NRW, Germany.

Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

出版信息

Exp Hematol Oncol. 2024 Oct 28;13(1):105. doi: 10.1186/s40164-024-00576-6.

Abstract

The basic idea of modulating the immune system to better recognize and fight tumor cells has led to the successful introduction of adoptive cellular immunotherapy (ACT). ACT-based treatment regimens, in which the patient's own immune cells are isolated and subsequently expanded (ex vivo) and reinfused, have also contributed significantly to the development of a personalized treatment strategy. Complementing this, the unprecedented advances in ACTs as chimeric antigen receptor (CAR)-T cell therapies and their derivatives such as CAR-NK, CAR-macrophages, CAR-γδT and CAR-NKT have further maximized the therapeutic outcomes. Herein, we provide a comprehensive overview of the development of ACTs in multiple myeloma (MM) and outline how they have evolved from an experimental form to a mainstay of standard clinical settings. Besides, we provide insights into cytokine-induced killer cell (CIK) therapy, an alternative form of ACT that (as CIK or CAR-CIK) has enormous potential in the clinical spectrum of MM. We also summarize the results of the major preclinical and clinical studies of adoptive cell therapy in MM and address the current challenges (such as cytokine release syndrome (CRS) and neurotoxicity) that limit its complete success in the cancer landscape.

摘要

调节免疫系统以更好地识别和对抗肿瘤细胞的基本理念已成功催生了过继性细胞免疫疗法(ACT)。基于ACT的治疗方案,即分离患者自身的免疫细胞,随后进行(体外)扩增并重新注入体内,也为个性化治疗策略的发展做出了重大贡献。与此相辅相成的是,作为嵌合抗原受体(CAR)-T细胞疗法及其衍生物(如CAR-NK、CAR-巨噬细胞、CAR-γδT和CAR-NKT)的ACT取得了前所未有的进展,进一步最大化了治疗效果。在此,我们全面概述了ACT在多发性骨髓瘤(MM)中的发展,并概述了它们如何从一种实验形式演变为标准临床环境的支柱。此外,我们深入探讨了细胞因子诱导的杀伤细胞(CIK)疗法,这是ACT的一种替代形式,(作为CIK或CAR-CIK)在MM的临床领域具有巨大潜力。我们还总结了MM过继性细胞疗法的主要临床前和临床研究结果,并探讨了目前限制其在癌症领域完全成功的挑战(如细胞因子释放综合征(CRS)和神经毒性)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc98/11514856/44a4ab81529d/40164_2024_576_Fig1_HTML.jpg

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