Chimeric Antigen Receptor-Macrophages in Pancreatic Cancer: Promise, Pitfalls, and the Path Ahead.

Chimeric antigen receptor-engineered macrophages (CAR-Ms) are emerging as a transformative frontier in immunotherapy and represent a promising strategy for pancreatic cancer. Unlike chimeric antigen receptor T-cell (CAR-T) or chimeric antigen receptor natural killer cell (CAR-NK) cells, which encounter limitations when applied to solid tumors, CAR-Ms combine innate tumor-homing capabilities with engineered antigen specificity to overcome these barriers. Recent studies have demonstrated encouraging antitumor activity in preclinical pancreatic ductal adenocarcinoma (PDAC) models; however, key questions remain regarding the persistence, safety, and scalability of these models. Nonetheless, despite these uncertainties, CAR-Ms may represent a paradigm shift from immune activation focused solely on direct cytotoxicity to one that also integrates immune orchestration and tumor microenvironmental reprogramming.