Jing Jiajie, Chen Yueming, Chi Enjie, Li Sisi, He Yilin, Wang Bingyan, Shen Hongqiang, Fan Liming, Wang Jiadong, Shangguan Tianli, Ge Xinyang, Jiang Yuhao, Chen Yangyu, Xu Chunjing
Departement of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, China.
Institute of Translational Medicine, Hangzhou City University, Hangzhou, China.
J Transl Med. 2025 Oct 28;23(1):1182. doi: 10.1186/s12967-025-07115-9.
Chimeric antigen receptor (CAR) therapy represents an innovative form of targeted treatment that employs genetically engineered effector cells to selectively target tumor cells. CAR-T immunotherapy, which uses T cells as effector cells, has demonstrated remarkable efficacy in hematological malignancies. However, its clinical application in solid tumors remains limited due to challenges such as poor tumor infiltration, cytokine release syndrome (CRS), neurotoxicity, off-target effects, and other adverse events. To address these limitations, CAR-engineered natural killer (CAR-NK) cells and macrophages (CAR-M) have been developed. Macrophages, as crucial components of innate and adaptive immunity, exhibit superior tumor microenvironment infiltration and long-term persistence, making them a promising tool for next-generation cancer immunotherapy. This review highlights the construction strategies and preclinical and clinical studies of CAR-M, comprehensively introduces the anti-tumor mechanisms, discusses their advantages and disadvantages compared with other CAR-engineered effector cells, and explores the challenges and prospects for CAR-M in treating solid tumors.
嵌合抗原受体（CAR）疗法是一种创新的靶向治疗形式，它利用基因工程改造的效应细胞来选择性地靶向肿瘤细胞。以T细胞作为效应细胞的CAR-T免疫疗法在血液系统恶性肿瘤中已显示出显著疗效。然而，由于肿瘤浸润差、细胞因子释放综合征（CRS）、神经毒性、脱靶效应和其他不良事件等挑战，其在实体瘤中的临床应用仍然有限。为了解决这些局限性，已开发出CAR工程化自然杀伤（CAR-NK）细胞和巨噬细胞（CAR-M）。巨噬细胞作为固有免疫和适应性免疫的关键组成部分，表现出卓越的肿瘤微环境浸润能力和长期持久性，使其成为下一代癌症免疫治疗的有前途的工具。本综述重点介绍了CAR-M的构建策略以及临床前和临床研究，全面介绍了其抗肿瘤机制，讨论了与其他CAR工程化效应细胞相比的优缺点，并探讨了CAR-M在治疗实体瘤方面的挑战和前景。
