CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Navigating the frontier of CAR-T cell resistance: From underlying mechanisms to innovative therapeutic solutions.
Navigating the frontier of CAR-T cell resistance: From underlying mechanisms to innovative therapeutic solutions.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
嵌合抗原受体（CAR）-T细胞疗法在治疗复发/难治性血液系统恶性肿瘤方面取得了显著成功，尤其是急性B淋巴细胞白血病（B-ALL）、B细胞淋巴瘤（BCL）和多发性骨髓瘤（MM）。然而，血液系统恶性肿瘤中的耐药性以及实体瘤中有限的免疫应答仍然是CAR-T 细胞疗法面临的主要挑战。肿瘤抗原丢失或调节、凋亡信号失调、CAR-T 细胞内在功能障碍以及肿瘤微环境（TME）中的免疫抑制成分显著损害了治疗效果。因此，了解介导CAR-T 细胞疗法耐药的机制并探索克服治疗失败的策略对于优化临床结果至关重要。本综述系统阐述了CAR-T 细胞疗法耐药的机制，并讨论了潜在的对策，包括双靶向策略、创新的CAR工程策略、TME重编程以及联合免疫疗法。
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of relapsed or refractory hematological malignancies, particularly acute B-cell lymphoblastic leukemia (B-ALL), B-cell lymphoma (BCL), and multiple myeloma (MM).
However, resistance in hematological malignancies and limited immune responses in solid tumors remain major challenges for CAR-T cell therapy. Tumor antigen loss or modulation, dysregulated apoptotic signaling, CAR-T cell-intrinsic dysfunction, and immunosuppressive components within the tumor microenvironment (TME) significantly compromise therapeutic outcomes.
Therefore, understanding the mechanisms that mediate resistance to CAR-T cell therapy and exploring strategies to overcome therapeutic failure are crucial for optimizing clinical results. This review systematically elucidates the mechanisms underlying resistance to CAR-T cell therapy and discusses potential countermeasures, including dual-targeted approaches, innovative CAR engineering strategies, TME reprogramming, and combination immunotherapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
