Abstract
BACKGROUND: The efficacy of chimeric antigen receptor natural killer (CAR-NK) cells in treating solid tumors is often limited, primarily due to the tumor microenvironment (TME), which hinders the recognition and infiltration of CAR-NK cells. Radiotherapy has been shown to modify the TME, enhance immune cell infiltration, and improve the recognition of tumor cells by immune cells. This study aimed to investigate the effects of combining radiotherapy with CAR-NK cells in a solid tumor model. METHODS: The Robo1 CAR-NK92 cell line was developed to specifically target Robo1. Tumor cell lines were generated following radiotherapy, and the cytotoxicity and infiltration of Robo1 CAR-NK92 cells in solid tumor models were evaluated both in vitro and in vivo post-radiotherapy. RESULTS: The cytotoxicity of Robo1 CAR-NK92 cells against tumor cells was significantly enhanced following radiotherapy, likely due to the upregulation of NKG2D ligands on the surface of the tumor cells. Furthermore, tumor cells post-radiotherapy were found to promote the migration of Robo1 CAR-NK92 cells. In in vivo experiments, the combination of radiotherapy and Robo1 CAR-NK92 cells resulted in prolonged survival and improved tumor control in a solid tumor mouse model. CONCLUSION: Our results indicate that the combination of Robo1 CAR-NK92 therapy and radiotherapy may present a promising approach for the treatment of solid tumors.