**5.3 CAR-macrophages**

CAR (Chimeric Antigen Receptor) macrophages are a type of genetically modified macrophages that have been engineered to enhance their phagocytic ability. CAR macrophages are created by introducing a CAR gene into the macrophages, which codes for a chimeric antigen receptor. This CAR allows the macrophages to specifically target and phagocytize specific cells, such as cancer cells, by recognizing specific antigens present on their surface [79]. The goal of this technology is to create a new way to fight cancer and other diseases by harnessing the natural abilities of macrophages to engulf and destroy unwanted cells.

CAR-M therapies have demonstrated the ability to eliminate tumor cells both in vitro and in preclinical in vivo models. In vitro, human CAR-M have been shown to exhibit antigen-specific phagocytosis, as well as secretion of cytokines/chemokines and the ability to kill target antigens [79]. In two immunodeficient NSG xenograft models, a single dose of anti-HER2 CAR-M significantly reduced the burden of tumors and prolonged overall survival against HER2+ SKOV3 tumors. Additionally, CAR-M that were administered intravenously (IV) were found to localize to tumors in several xenograft models and persisted in tumor-free mice (primarily within the liver) for at least 62 days, as detected by whole-body bioluminescent imaging. In vitro analysis further demonstrated that CAR-M were capable of coordinating an antitumor T cell response by recruiting T cells and cross-presenting antigens from phagocytosed cells [19, 86, 87].
