Salmonella vector creates de novo parvovirus that reduces solid tumors and forms antitumor immune memory.

Abstract

We have created a Salmonella vector that delivers oncolytic viruses (OVs) into solid tumors. Despite their potential, OVs are cleared after systemic injection and are not effective against internal tumors. When injected intravenously, virus-delivering Salmonella (VDS) is safe and colonizes tumors 50 million times more than clearance organs. After colonization, VDS invades cancer cells, releases a virus-encoding plasmid, and initiates virion formation. Bacterial delivery of the H-1 parvovirus reduces both hepatocellular and pancreatic tumors, increases survival, and triggers the formation of tumor-specific splenocytes that prevent re-implantation. Treating with VDS increases dendritic cells, infiltration of CD8 T cells, and polarized macrophages. Intravenous injection of VDS produces the same responses as an intratumoral injection, and outperforms direct injection of H-1 parvovirus (H-1PV), which minimally affects immune responses and tumor volume. Combining bacteria and OVs creates a therapy that activates the immune system, generates antitumor immunity, and provides a promising platform for treating solid tumors.