Wu Anran, Zhang Tingying, Yu Hongkai, Cao Yuyue, Zhang Rui, Shao Ruonan, Liu Bofeng, Chen Liting, Xu Kailin, Chen Wei, Ho Jinyuan, Shi Xiaofeng
Department of Hematology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210003, China; The Second Clinical Medical School of Nanjing Medical University, Nanjing 210011, China.
Department of Hematology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210003, China.
Cytokine Growth Factor Rev. 2025 Jun;83:66-76. doi: 10.1016/j.cytogfr.2025.04.002. Epub 2025 Apr 22.
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a revolutionary approach in the treatment of hematological malignancies, including acute lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma. Despite its promise, the clinical efficacy is often hampered by transient efficacy and subsequent relapse, which curtail the long-term success of this treatment. Current research focuses on overcoming these obstacles by exploring multitarget strategies and optimizing CAR-T cell design. This review summarizes recent insights into the resistance mechanisms associated with CAR-T cell therapy, and delineates emerging strategies for optimized CAR construction, including targeting multiple antigens, improving CAR design, and enhancing T-cell persistence. The goal is to provide a comprehensive overview of the field's current landscape to guide future research and the clinical application of CAR-T cell therapies.
嵌合抗原受体（CAR）T细胞疗法已成为治疗血液系统恶性肿瘤（包括急性淋巴细胞白血病、B细胞淋巴瘤和多发性骨髓瘤）的一种革命性方法。尽管前景广阔，但临床疗效常常受到短暂疗效和随后复发的阻碍，这限制了该疗法的长期成功。目前的研究集中在通过探索多靶点策略和优化CAR-T细胞设计来克服这些障碍。本综述总结了与CAR-T细胞疗法相关的耐药机制的最新见解，并阐述了优化CAR构建的新策略，包括靶向多种抗原、改进CAR设计和增强T细胞持久性。目的是全面概述该领域的当前状况，以指导未来的研究和CAR-T细胞疗法的临床应用。
