Allogeneic melanoma vaccine expressing alphaGal epitopes induce anti-tumor immunity to autologous melanoma antigens without signs of toxicity (48.7)

Abstract

Abstract The hyperacute rejection of a xenotransplant is a potent mechanism of tissue destruction mediated by complement-fixing natural Ab that recognize alphaGal (aGal) epitopes. These epitopes are not present on human cells. Humans develop high titers of naturally acquired Ab against these epitopes. We hypothesized that this mechanism could be used to generate a potent anti-cancer vaccine. In this study we tested this hypothesis by using an allogeneic whole cell cancer vaccine to treat murine melanoma. We used the aGal KO mice (aGT H-2bb) and the aGal negative melanoma cell lines B16 and S91M3. We genetically engineered S91M3 (H-2dd) cells to produce the aGal(+)S91M3 cells. Mice with pre-existing subcutaneous and pulmonary B16 (H-2bb) tumors were efficiently treated with aGal(+)S91M3 melanoma vaccines. Control S91M3 vaccines had no impact on tumor growth. Vaccination with aGal(+)S91M3 induced cytotoxic CD8+ T cells recognizing the “autologous” aGal(-)B16 tumors measured by IFN-gamma release and by adoptive transfer experiments. The presence of allo-antigens did not dominate the induction of immunity to “cryptic” tumor antigens tested in the pre-existing melanoma metastasis model. The effective anti-tumor immunity was not associated with autoimmunity or other signs of toxicity in long-term toxicology studies for breast, lung and melanoma allogeneic vaccines. This study establishes for the first time the safety and efficacy data of allogeneic aGal(+) whole cell vaccines and constituted the basis for the initiation of human clinical trials to treat human cancers currently underway.