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嵌合抗原受体T细胞疗法治疗多发性骨髓瘤:一种令人鼓舞的细胞疗法。

CAR-T cells in the treatment of multiple myeloma: an encouraging cell therapy.

作者信息

Yu Tong, Jiao Jian-Hang, Wu Min-Fei

机构信息

Department of Orthopaedic Medical Center, The Second Norman Bethune Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Front Immunol. 2025 Feb 26;16:1499590. doi: 10.3389/fimmu.2025.1499590. eCollection 2025.

Abstract

Multiple myeloma (MM) is a malignant disease of plasma cells that accounts for approximately 10% of all hematological malignancies and is characterized by a clonal proliferation of malignant plasma cells in the bone marrow. Numerous therapeutic strategies, including proteasome inhibitors, immunomodulators, monoclonal antibodies against CD38 and autologous stem cell transplantation, have prolonged the median survival of MM patients. Nevertheless, almost all MM patients suffer disease relapses due to drug resistance and eventually die from MM or MM-related complications. Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy strategy for MM and has shown encouraging results in several clinical trials. However, the use of CAR T-cell therapy for the treatment of MM is still associated with several difficulties, including antigen escape, poor persistence, an immunosuppressive microenvironment, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, CAR T-cell-associated encephalopathy syndrome, cytopenia, and infections. In this review, we describe in detail the target antigens of CAR T cells in MM. We also comprehensively discuss recent innovations in the development of CAR T cells to improve clinical efficacy and strategies to overcome the limitations of CAR T-cell therapy in MM.

摘要

多发性骨髓瘤(MM)是一种浆细胞恶性疾病,约占所有血液系统恶性肿瘤的10%,其特征是骨髓中恶性浆细胞的克隆性增殖。包括蛋白酶体抑制剂、免疫调节剂、抗CD38单克隆抗体和自体干细胞移植在内的多种治疗策略,延长了MM患者的中位生存期。然而,几乎所有MM患者都会因耐药而出现疾病复发,最终死于MM或MM相关并发症。嵌合抗原受体(CAR)T细胞疗法是一种针对MM的新型免疫治疗策略,已在多项临床试验中显示出令人鼓舞的结果。然而,使用CAR T细胞疗法治疗MM仍存在一些困难,包括抗原逃逸、持久性差、免疫抑制微环境、细胞因子释放综合征、免疫效应细胞相关神经毒性综合征、CAR T细胞相关脑病综合征、血细胞减少和感染。在本综述中,我们详细描述了MM中CAR T细胞的靶抗原。我们还全面讨论了CAR T细胞开发中的最新创新,以提高临床疗效,以及克服MM中CAR T细胞疗法局限性的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/11897482/d9a2926b3a0e/fimmu-16-1499590-g001.jpg

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