Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer
Yizhao Chen, Qianling Xin, Mengjuan Zhu, Jiaqi Qiu, Yan Luo, Ruilin Li, Wei Wei, Jiajie Tu
Abstract
This review summarizes recent advances in the CAR-Macrophage technology platform for the treatment of non-tumor diseases, highlighting the critical role of chimeric antigen receptor structural design in CAR-Macrophage therapy. • We have outlined the development path of chimeric antigen receptor macrophage (CAR-M) technology, from tumors to non-tumor diseases. • We have comprehensively summarized the research status of CAR-M therapy in non-tumor diseases. • The advantages and disadvantages of CAR-M therapy in various non-tumor diseases were evaluated. • The important impact of CAR intracellular domain on therapeutic effects is discussed. • Factors affecting the application of CAR-M in non-tumor diseases are considered. After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, the first approved CAR cell therapy product, has demonstrated therapeutic potential in treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach in CAR immune cell therapy, particularly for solid tumor treatment, highlighting the feasibility of using macrophages to eliminate pathogens and abnormal cells. This review summarizes the progress of CAR-M therapy in non-tumor diseases and discusses various CAR intracellular activation domain designs and their potential to optimize therapeutic effects by modulating interactions between cellular components in the tissue microenvironment and CAR-M. Additionally, we discuss the characteristics and advantages of CAR-M therapy compared to traditional medicine and CAR-T/NK therapy, as well as the challenges and prospects for the clinical translation of CAR-M. This review provides a comprehensive understanding of CAR-M for the treatment of non-tumor diseases, analyzes the advantages and characteristics of CAR-M therapy, and highlights the important impact of CAR intracellular domain design on therapeutic efficacy. In addition, the challenges and clinical translation prospects of developing CAR-M as a new cell therapy are discussed.