IDENTIFICATION OF NEOANTIGENS RELEASED BY SALMONELLA-INFECTED TUMOR CELLS FOR A NOVEL APPROACH TO CANCER IMMUNOTHERAPY

“Identification of neoantigens released by Salmonella-infected tumor cells for a novel approach to cancer immunotherapy” Advancement in cancer immunotherapy has revealed the importance of targeting neoantigens: tumor specific antigens that prompt a strong antitumor response escaping from the central T tolerance. Our laboratory has previously shown that infection of mouse tumor cell lines with Salmonella induces the transfer of antigens between adjacent cells, specifically through hemichannels. Now we demonstrate that Salmonella not only leads to the transfer of immunogenic antigens between adjacent cells but also the release of peptides in the extracellular milieu. A mass spectrometry analysis of proteins and peptides released by infected murine melanoma cells revealed that among them there are novel tumor epitopes and potential neoantigens. We tested the released peptides as components of a vaccine formulation given to prevent tumor progression in a murine model of melanoma and we demonstrated that are immunogenic. We attested that also human melanoma cell lines infected with Salmonella release peptides; these induce the expansion of CD8-T cell from peripheral blood mononuclear cells that specifically kill human melanoma cells in vitro. We propose the treatment with Salmonella of patients-derived tumor cells as a strategy to obtain neoantigens that could be applied in clinical studies as a vaccine formulation. Encouraging preliminary results have been obtained with the therapeutic treatment of pet dogs with spontaneous osteosarcoma and high grade sarcoma with a vaccine formulation based on peptides released by their own tumor cells following Salmonella infection.