CAR-macrophages in solid tumors: promise, progress, and prospects

Abstract Chimeric antigen receptor macrophages (CAR-Ms) represent a promising frontier in immunotherapy, leveraging both innate and engineered capabilities to combat solid tumors. CAR-Ms can actively remodel the tumor microenvironment while directly targeting tumor cells through CAR signaling, making them a potential alternative to existing cell-based therapies. Pre-clinical and clinical evidence suggests that CAR-M therapy holds significant promise for treating solid tumors. However, its clinical translation remains challenging due to restricted cell expansion, genetic engineering complexities, and variability in product quality. This article reviews recent advances in the CAR-M field, discussing the biological rationale behind this approach, key preclinical findings, and technological innovations necessary to facilitate clinical success as a versatile, off the shelf immunotherapy for hard-to-treat solid malignancies.