Local Delivery of SBRT and IL12 by mRNA Technology Overcomes Suppressive Barriers to Eliminate Pancreatic Cancer

The immunosuppressive milieu in PDAC tumors has proven a significant hurdle to new and existing treatments, resulting in survival statistics that have barely changed in the last 5 decades. Here we present a novel combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly to the tumor of murine models of PDAC.

This treatment was effective against primary and metastatic models of PDAC, leading to a dramatic reduction in tumor growth and even achieving cures in both settings. IL-12 protein concentrations were transient and remained localized primarily to the tumor. Depleting CD4 and CD8 T cells abrogated treatment efficacy, confirming these cells were the key players in the anti-tumor immune response generated.