Opsonization and timing as key determinants of MBTA immunotherapy efficacy in pancreatic adenocarcinoma and recurrence treatment

BACKGROUND: Pancreatic adenocarcinoma is a highly aggressive cancer with very limited treatment options. This study aimed to optimize the efficacy of a previously developed tumor immunotherapy for the treatment of this disease and its recurrences. METHODS: Mouse models of pancreatic and colon adenocarcinoma were established using Panc02 and MC38 cells, respectively. Tumors were treated by intratumoral administration of MBTA, a formulation containing resiquimod, poly(I:C), LTA, anti-CD40 antibody, and mannan-BAM (a phagocytosis-stimulating mannan anchored to the tumor cell membrane via a biocompatible membrane anchor, BAM). Multiple variants of the therapy were tested, differing in composition and timing, including treatment of recurrences. RESULTS: Intratumoral MBTA immunotherapy administered using an optimized 5 × 2 schedule resulted in an 87.5% survival rate in mice bearing subcutaneous Panc02 tumors. MBTA immunotherapy also effectively treated spontaneous local Panc02 recurrences that developed in a small subset of mice. High efficacy of MBTA was further confirmed in a murine model of colon adenocarcinoma. CONCLUSION: These findings suggest that MBTA is a promising therapeutic approach for primary and recurrent pancreatic adenocarcinoma, with potential for broader clinical application.