Vaccination with Mimotopes Prevents Tumor Growth by Enhancing the Activation of T cells that Respond to Natural Tumor Antigens (41.40)

Abstract

Abstract Vaccination with mimotopes, or peptide mimics of self-tumor antigens, is a potential strategy for antigen-specific immunotherapy of cancer. We tested mimotopes with substitutions in residues involved in T cell interactions, rather than in conventional MHC-anchor residues, for protection against the transplantable tumor, CT26. Although vaccination with all of the mimotopes elicited tumor-specific T cells more effectively than the wild type tumor antigen, AH1, only some mimotopes prevented tumor growth. Vaccination with the protective mimotopes generated considerably more cross-reactive T cells that produced the cytokine IFNgamma after stimulation with lower concentrations of the AH1 peptide. These T cells expressed TCR molecules with a more restricted Vbeta repertoire ex vivo, but were similar in CDR3 sequence to the T cells generated by vaccination with the AH1 peptide. Importantly, the T cells responding to the non-effective mimotopes did not inhibit the antitumor responses of the protective mimotopes. These results suggest that protective mimotopes generate antitumor immunity, in part, by enhancing the activation and differentiation of a subset of T cells that naturally respond to the tumor, not a new repertoire of T cells only elicited by the mimotope.