[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。

[Abstract] 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.

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）