Role of CAR-T Cell Therapy in Pancreatic cancer: An Updated Narrative Review of Current Evidence.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy projected to become the second leading cause of cancer-related deaths in the United States by 2030. Despite advances in surgery, chemotherapy, and radiotherapy, survival remains poor due to late diagnosis and treatment resistance. Immunotherapy, particularly checkpoint inhibitors, has shown limited benefit in PDAC, underscoring the need for innovative strategies. Chimeric antigen receptor T cell (CAR-T) therapy, a form of adoptive immunotherapy, has revolutionized treatment for hematologic malignancies and is now being investigated in solid tumors, including PDAC. This narrative review examines 74 articles selected from PubMed and Google Scholar, focusing on CAR-T cell therapy in pancreatic cancer. PDAC's aggressive nature and resistance to conventional therapies highlight the urgency for novel interventions. CAR-T cells are genetically engineered to recognize tumor antigens independently of major histocompatibility complex presentation, with second-generation designs being the most utilized. Early clinical trials targeting mesothelin, HER2, and other tumor-associated antigens show promise but face challenges related to T-cell persistence, trafficking, and tumor immune evasion. Advances in CAR-T engineering continue to enhance their potential against solid tumors. While obstacles remain, CAR-T cell therapy represents a promising frontier in the management of PDAC, with ongoing research poised to improve patient outcomes.