Key lab of Artificial Organs and Computational Medicine, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, Zhejiang, 310015, China.
Department of Immunology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
Mol Cancer. 2024 Jun 1;23(1):117. doi: 10.1186/s12943-024-02032-9.
Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.
在过去的十年中，嵌合抗原受体（CAR）-T 疗法在血液癌症的应用方面取得了重大进展。然而，其在治疗实体瘤方面的效果仍然不足，需要探索替代免疫疗法来克服当前 CAR-T 细胞面临的重大挑战。随着巨噬细胞的出现，CAR 为基础的针对实体瘤的免疫疗法显示出了前景，巨噬细胞具有强大的吞噬能力、抗原呈递功能，并且能够改变肿瘤微环境并刺激适应性反应。本文全面介绍了 CAR-M 治疗的最新进展，涵盖了基础科学研究和临床试验。本研究探讨了阻碍 CAR-M 治疗充分发挥潜力的主要障碍，以及可以用来克服这些障碍的潜在策略。随着原位基因修饰、合成生物学技术和生物材料支持的基因转移等革命性技术的出现，为操纵肿瘤相关巨噬细胞提供了更多的资源，我们认为，结合这些先进的方法将开创 CAR-M 治疗的新时代，展现出更好的疗效、安全性和可用性。
