Proto-oncogene products as target antigens for cancer vaccines

Abstract

Enthusiasm for cancer vaccines has undoubtedly been fueled by the success of vaccines against infectious diseases. The underlying principle of antibacterial or antiviral vaccines is the induction of an immune response to foreign (non-self) antigen(s) encoded by the invading microorganism. Until recently, the premise of a response to nonself antigen would have seemed the sine qua non of any vaccine, so self evident as to scarcely merit remark. In fact, the vaccine concept discussed here eschews this premise in favor of a response to self antigen as an anti-tumor modality. Vaccination would target proteins encoded by protooncogenes. As measured relative to their expression in normal cells, proto-oncogene-encoded proteins are overexpressed in the tumor cells of a number of human cancers. Any vaccine intended to target self antigen must manage to both circumvent a possible tolerogenicity of the antigen and, at the same time, avoid the induction of autoimmune pathology. For the vaccine concept discussed here, the difference in levels of proto-oncogene expression between tumor cells and normal cells provides a basis for satisfying both of these requirements and hence a basis for the immune-mediated destruction of tumor tissue.