Abstract B29: Improving the identification of beneficial mimotopes using a representative tumor-specific T cell receptor

Vaccination with peptide mimotopes is a promising strategy to improve antitumor immunity. Mimotopes function by eliciting increased numbers of T cells that cross-react with the native tumor antigen. Using a high affinity tumor-specific T cell clone (CT), we have identified a panel of mimotopes for the dominant antigen (AH1) of a mouse colon tumor cell-line (CT26) that elicits a range of tumor protection when used in vaccines. Ex vivo evaluation of the TCRs of T cells initiated by mimotopes that protect against tumor challenge revealed increased representation of a Vβ8.3/Jβ2.6 motif: a small hydrophobic amino acid, followed by a large polar residue, and the tyrosine of the Jβ2.6. Clonotypes with this motif were also identified within the AH1-specific T cell repertoire of naturally responding TIL and following vaccination with the AH1 antigen. This motif was not found in the original CT clone. One particular clone with the motif made up nearly 8.5% of all Vβ8.3 sequences identified following immunization with mimotopes. Thus, we tested the hypothesis that this ‘representative’ TCR improves the frequency of discovery of efficacious mimotopes for cancer immunotherapy relative to the high affinity CT clone in the CT26 model. We have demonstrated that this is the case by screening genetically encoded peptide libraries. These results have important implications when considering the optimal T cells responding to tumor antigens and the improved identification of mimotopes for cancer immunotherapy. Citation Format: Jill E. Slansky, Jonathan D. Buhrman. Improving the identification of beneficial mimotopes using a representative tumor-specific T cell receptor. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B29.