CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR T-cell therapy in hematologic and solid malignancies: mechanisms, clinical applications, and future directions.
CAR T-cell therapy in hematologic and solid malignancies: mechanisms, clinical applications, and future directions.
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嵌合抗原受体(CAR)T细胞疗法代表了一种治疗恶性肿瘤的突破性方法。这种免疫疗法涉及对T细胞进行基因修饰,以靶向并消灭肿瘤细胞,在多种癌症中均显示出有效性。其显著的特异性、实体瘤浸润能力以及持久的缓解反应,凸显了其彻底变革癌症治疗的潜力。通过靶向特定的肿瘤抗原,CAR-T 细胞疗法最大限度地减少了脱靶效应,并实现了个性化治疗。目前已有六种CAR-T 细胞疗法获得批准,展现出卓越的疗效,尤其是在B细胞恶性肿瘤和多发性骨髓瘤方面。然而,细胞因子释放综合征、神经毒性,以及由于抗原不可靠、肿瘤核心缺氧和免疫抑制环境等问题导致的实体瘤靶向困难等挑战,使其应用变得复杂。解决这些问题需要创新策略,以提高CAR-T 细胞的疗效并降低毒性。本综述详细介绍了CAR-T 细胞的工程化改造、信号通路、在B细胞恶性肿瘤中的临床成功、在实体瘤中面临的挑战、新兴策略以及安全性管理。
Chimeric antigen receptor (CAR) T-cell therapy represents a groundbreaking approach to treating malignancies. This immunotherapy involves genetic modification of T cells to target and eliminate tumor cells, proving effective across various cancers. Its remarkable specificity, solid tumor infiltration, and durable responses highlight its potential to revolutionize cancer treatment.
By targeting specific tumor antigens, CAR-T-cell therapy minimizes off-target effects and enables personalized treatment. Six CAR-T-cell therapies have been authorized, showing exceptional effectiveness, particularly for B-cell malignancies and multiple myeloma.
However, challenges such as cytokine-release syndrome, neurotoxicity, and difficulties in targeting solid tumors due to issues like unreliable antigens, hypoxic tumor cores, and immunosuppressive environments complicate its application. Addressing these requires innovative strategies to enhance CAR-T cell efficacy and reduce toxicity. This review details CAR T-cell engineering, signaling pathways, clinical successes in B-cell malignancies, challenges in solid tumors, emerging strategies, and safety management.
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