Harnessing the potential of CAR-NK cell therapy in gastrointestinal cancers: From bench to bedside

Cancer is one of the leading causes of mortality worldwide, with gastrointestinal (GI) malignancies being among the most prevalent and lethal types. Traditional treatments for GI cancers, such as chemotherapy and radiotherapy, often result in severe side effects due to their lack of specificity. Among the various therapeutic strategies, immunotherapy has emerged as a promising and highly specific approach for treating GI cancers. Immunotherapeutic methods include the use of monoclonal antibodies with diverse specificities, as well as cell-based therapies. Engineered cell therapies, particularly those utilizing chimeric antigen receptor (CAR) T cells and natural killer (NK) cells, represent a forefront in innovative cancer treatment. While CAR-T cells have shown promise, CAR-NK cells offer distinct advantages, such as the ability to kill tumor cells independently of CAR signaling and their suitability for safe allogeneic transplantation.Given these benefits, CAR-NK cells have gained attention as either a complementary or alternative strategy to CAR-T cell therapy in GI cancers. Despite this potential, a comprehensive review specifically focused on CAR-NK therapy in GI malignancies has been lacking. The present study aims to address this gap by exploring the application of CAR-NK therapy in various GI cancers, including colorectal, pancreatic, hepatocellular, esophageal, gastric, and tongue cancers, highlighting the targeted tumor antigens and recent advancements in the field.