Delivery of a genetic cancer vaccine containing a small molecule inducible immune adjuvant by in vivo electroporation (eVac) (P4332)

Abstract The use of dendritic cell vaccines to treat cancer has significant potential, however that potential has yet to be achieved in treating patients. Fortunately, pioneering biotechnologies are paving the way for more effective cancer vaccines. Our lab has developed a drug inducible MyD88/CD40 (iMC) composite adjuvant that promotes robust cytotoxic T cell priming in iMC activated DCs. Despite the iMC innovation, the use of patient-tailored ex vivo DC vaccines is impractical for widespread use, due to issues of scalability and cost. We have therefore begun to address the delivery of DC vaccines as “off-the-shelf” therapies using in vivo electroporation (EP) of plasmid DNA (pDNA) encoding both the iMC adjuvant and tumor antigen (eVac). Intradermal EP of pDNA encoding the model antigen LacZ in mice suggests that LacZ-specific T cell responses were induced, as mice receiving LacZ + EP prophylactically were either protected from establishment of B16/LacZ tumors or demonstrated significantly slower tumor growth compared to controls. In mice bearing pre-established B16/LacZ tumors, LacZ-eVac, but not EP with LacZ antigen alone significantly reduced tumor burden and increased survival. Taken together, these data indicate that eVac with iMC-antigen is an effective “off-the-shelf” cancer vaccine. These findings warrant elucidation of the underlying immunological mechanisms responsible for the anti-tumor responses observed with eVac treatment to guide further refinement of the vaccine.