CAR-T细胞治疗的临床关键问题和对策  

Clinical key issues and countermeasures of CAR-T cell therapy

作　　者：陈新峰[1] 刘莎莎[1] 张毅[1] CHEN Xinfeng;LIU Shasha;ZHANG Yi(Biotherapy Center/Biological Immunotherapy Ward,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan,China)

机构地区：[1]郑州大学第一附属医院、生物细胞治疗中心/生物免疫治疗病区,河南郑州450052

出　　处：《中国肿瘤生物治疗杂志》2025年第1期9-13,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金(No.U24A20734,No.82370227);河南省中央引导地方科技发展资金项目(No.Z20221343036)。

摘　　要：自2017年以来,已有12款嵌合抗原受体基因修饰T淋巴细胞(CAR-T细胞)产品相继被批准用于血液系统恶性肿瘤的治疗,包括复发性/难治性急性B淋巴细胞白血病、特定亚型B细胞淋巴瘤和多发性骨髓瘤。然而,CAR-T细胞疗法在应用过程中面临诸多挑战,如在治疗血液系统肿瘤中的抵抗、生产周期长、个体化/价格昂贵,在实体瘤中的肿瘤异质性强/抗原逃逸、浸润能力不足、免疫抑制微环境和反应性差等问题。随着肿瘤免疫学研究的深入和基因工程技术的发展,尝试了众多新策略来提升CAR-T细胞疗法的疗效和普适性。作者根据自身对该领域研究的认知,针对CAR-T细胞疗法的临床关键问题及其应对解决策略进行述评,为未来CAR-T细胞疗法的基础研究和临床转化提供重要思路。Since 2017,twelve chimeric antigen receptor gene-modified T lymphocyte(CAR-T cell)products have been approved for the treatment of hematological malignancies,including relapsed/refractory acute B lymphoblastic leukemia(B-ALL),specific subtypes of B cell lymphoma,and multiple myeloma.However,CAR-T cell therapy faces numerous challenges in its clinical application,such as resistance,lengthy production cycles,high individuation and costs in hematological tumors,and tumor heterogeneity/antigen escape,insufficient infiltration capability,immunosuppressive microenvironments,and poor therapeutic response in solid tumors.With the in-depth exploration of tumor immunology and the development of genetic engineering technology,various new strategies have been attempted to enhance the efficacy and generalizability of CAR-T cell therapy.This paper presents a commentary on CAR-T cell therapy,with a focus on key clinical issues and corresponding countermeasures,providing valuable insights for future basic research and clinical transformation of CAR-T cell therapy.

关 键 词：免疫治疗 嵌合抗原受体基因修饰T淋巴细胞 肿瘤微环境 实体瘤 

分 类 号：R730.51[医药卫生—肿瘤] R392.12[医药卫生—临床医学]