Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

Defined tumor-associated antigens (TAA) are attractive targets for anti-tum or immunotherapy. Here, we describe a novel genome-wide approach to identif y multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors were examined for gene expression by mRNA microarray scanning. This analysis rev ealed heterogeneity of the tumors in agreement with the assumption that the y represent different tumorigenic events. Several genes were overexpressed in one or more of the tumors. To examine whether overexpressed genes might be used to identify TAA, mice were immunized with mixtures of peptides repr esenting putative cytotoxic T cell epitopes derived from one of the gene pr oducts. Indeed, such immunized mice were partially protected against subseq uent tumor challenge. Despite being immunized with bona fide self antigens, no clinical signs of autoimmune reactions were observed. Thus, it appears possible to evaluate the entire metabolism of any given tumor and use this information rationally to identify multiple epitopes of value in the genera tion of tumor-specific immunotherapy We expect that human tumors express si milar tumor-specific metabolic imprints, which may be used to identify pati ent-specific arrays of TAA. This may enable a multi-epitope based immunothe rapy with improved prospects of clinical tumor rejection.