Lee Chaelin, Kwak Chaerin, Choi Minhyun, Kim Ahban, Kim Seongjin, Rhee Inmoo
Department of Bioscience and Biotechnology, Sejong University, Republic of Korea.
Department of Bioscience and Biotechnology, Sejong University, Republic of Korea.
Int Immunopharmacol. 2025 May 27;156:114720. doi: 10.1016/j.intimp.2025.114720. Epub 2025 Apr 26.
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.
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，旨在克服基于T细胞的CAR疗法在实体瘤治疗中的局限性。然而，由于肿瘤穿透性差以及肿瘤微环境（TME）中存在强烈的免疫抑制信号，CAR-T细胞在实体瘤中的疗效有限。CAR-M疗法已成为一种有前景的替代方案，可能克服这些局限性。CAR-M是经过工程改造的巨噬细胞，能够检测肿瘤抗原，使其在实体瘤中积聚，并通过吞噬作用破坏癌细胞。与CAR-T细胞不同，CAR-M可以重塑TME，并引发先天性和适应性免疫反应，同时细胞因子释放综合征（CRS）的风险较低。本文综述了目前工程化CAR-M的方法，并讨论了它们如何在TME中识别肿瘤抗原。我们还总结了CAR-M递送系统和功能设计的最新进展，并强调了评估基于CAR-M疗法的临床和临床前研究的现状。尽管仍存在局限性，但CAR-M疗法为实体瘤免疫治疗提供了一个有吸引力的平台，并且可能在未来癌症治疗中发挥越来越重要的作用。
