Robo1-specific CAR-NK Immunotherapy Enhances Efficacy of 125 I Seed Brachytherapy in an Orthotopic Mouse Model of Human Pancreatic Carcinoma.

Background/Aim: The aim of the current study was to investigate the synergistic efficacy of Robo1 bichimeric antigen receptor-natural killer cell (BiCAR-NK) immunotherapy and I-125 seed brachytherapy in an orthotopic pancreatic cancer mouse model. Materials and Methods: The orthotopic pancreatic tumor model was established with human pancreatic cancer BxPC-3 cells expressing red fluorescent protein. The mice were treated with I-125 seed implantation alone or the combination of I-125 seeds with Robo1-specific CAR-NK cells. To assess tumor inhibition, in vivo fluorescence imaging was conducted. 7 Tesla magnetic resonance (7T-MR) scanning was applied to measure the changes in the metabolic profiles of tumor tissues. Results: Tumor size was significantly reduced in the I-125 and I-125 +CAR-NK treated group compared to the untreated group (p<0.05). The I-125 seed +CAR-NK treated group showed significantly higher tumor reduction than I-125 seed treatment alone (p<0.05). T1 diffusion weighted imaging (T1DWI) sequence showed that the tumors of the I-125 +BiCAR-NK treated group had a significantly higher grey scale value than the tumors from the untreated control and the group treated with I-125 seed alone (p<0.05). Conclusion: Robo1 specific CAR-NK immunotherapy enhances efficacy of I-125 seed brachytherapy in an orthotopic pancreatic cancer mouse model.