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利用 CAR 巨噬细胞的髓系可塑性进行实体瘤免疫治疗

英文原题:Harnessing myeloid plasticity in CAR macrophages for solid tumor immunotherapy.

PubMed 2026/06/02(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

研究概要

嵌合抗原受体巨噬细胞(CAR-Ms)是一种新兴的髓系细胞疗法,旨在利用巨噬细胞在实体瘤中的固有可塑性。

中文摘要

嵌合抗原受体巨噬细胞(CAR-M)是一种新兴髓系细胞疗法,旨在利用巨噬细胞在实体瘤中的固有可塑性。CAR-M将抗原特异性识别与巨噬细胞介导的吞噬、抗原呈递和局部免疫重塑相结合,可协调肿瘤杀伤与肿瘤微环境重编程。CAR设计、细胞内信号、细胞平台和基因递送方面的进展,已使其能够在免疫功能完整模型中开展临床前评估,并进入早期临床研究。CAR-M可增强T细胞和NK细胞浸润、促进抗原扩展,并提高肿瘤对免疫检查点阻断的敏感性。包括靶向HER2的CT-0508在内的早期临床研究显示,CAR-M可行生产、安全性可接受,并能浸润肿瘤和重塑免疫环境,但客观疗效仍有限。主要挑战包括维持抗肿瘤极化状态、持久性、规模化生产、靶点选择及安全性控制。持续优化CAR-M设计并利用髓系细胞可塑性,对于实现其作为实体瘤免疫治疗平台的潜力至关重要。

展开英文摘要原文

Chimeric antigen receptor macrophages (CAR-Ms) are an emerging myeloid cell therapy designed to exploit the inherent plasticity of macrophages in solid tumors. By integrating antigen-specific recognition with macrophage-mediated phagocytosis, antigen presentation, and local immune remodeling, CAR-Ms coordinate tumor killing with reprogramming of the tumor microenvironment. Advances in CAR design, intracellular signaling, cellular platforms, and gene delivery have enabled preclinical evaluation in immunocompetent models and early clinical testing. CAR-Ms can enhance T cell and NK cell infiltration, promote antigen spreading, and sensitize tumors to immune checkpoint blockade. Early clinical studies, including HER2-targeted CT-0508, demonstrate feasible manufacturing, acceptable safety, tumor infiltration, and immune remodeling, though objective efficacy remains limited. Major challenges include maintaining antitumor polarization, persistence, scalable manufacturing, target selection, and safety control. Continued optimization of CAR-M design and exploitation of myeloid plasticity will be critical to realizing their potential as solid tumor immunotherapy platforms.

论文信息

作者
You Z、Lin Z、Zhang Y、Xu L、Zhang W
第一作者单位
The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.China
通讯作者单位
Department of immunology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Beijing Key Laboratory of Cell and Gene Therapy for Digestive System Cancers, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: zhangwen@cicams.ac.cn.China
文献类型
综述
期刊
Critical reviews in oncology/hematology2026 Sep
原文标识
PubMed 42235899 · DOI 10.1016/j.critrevonc.2026.105414