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:Advancing immunotherapy with innovations in CAR-M engineering for cancer treatment.
Advancing immunotherapy with innovations in CAR-M engineering for cancer treatment.
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嵌合抗原受体巨噬细胞(CAR-M)疗法正在成为一种有前景的免疫治疗策略,旨在克服实体瘤中T细胞CAR疗法的局限。CAR-T 细胞治疗实体瘤的疗效有限,原因包括肿瘤穿透能力差及肿瘤微环境(TME)强烈的免疫抑制信号。CAR-M疗法作为一种可能克服这些局限的替代方案应运而生。CAR-M是经工程化改造的巨噬细胞,可识别肿瘤抗原并在实体瘤中聚集,通过吞噬作用破坏癌细胞。与CAR-T 细胞不同,CAR-M可重塑TME并启动先天及适应性免疫应答,且细胞因子释放综合征(CRS)风险较低。本综述介绍当前CAR-M工程化策略,并讨论其如何在TME中识别肿瘤抗原;还总结CAR-M递送系统和功能设计的最新进展,并概述评估CAR-M疗法的临床和临床前研究现状。尽管仍存在局限,CAR-M疗法为实体瘤免疫治疗提供了有力平台,未来有望发挥日益重要的作用。
Chimeric antigen receptor macrophage (CAR-M) therapy is emerging as a promising immunotherapeutic strategy designed to overcome the limitations of T cell-based CAR therapies in solid tumors.
However, CAR-T cells have shown limited efficacy in solid tumors due to poor tumor penetration and strong immunosuppressive signals in the tumor microenvironment (TME). CAR-M therapy has emerged as a promising alternative that may overcome these limitations. CAR-Ms are engineered macrophages that detect tumor antigens, enabling their accumulation in solid tumors where they destroy cancer cells by phagocytosis.
Unlike CAR-T cells, CAR-Ms can remodel the TME and initiate innate and adaptive immune responses with lower risk of cytokine release syndrome (CRS). This review presents current approaches for engineering CAR-Ms and discusses how they engage tumor antigens within the TME.
We also summarize recent advances in CAR-M delivery systems and functional design and highlight the status of clinical and preclinical studies evaluating CAR-M-based therapies. Despite remaining limitations, CAR-M therapy provides a compelling platform for solid tumor immunotherapy and is likely to play an expanding role in future cancer treatment.
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