Identification Of Tumor-Specific Antigens Associated With Ret/Ptc3 Expression

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Relocated in transformation/papillary thyroid carcinoma, RET/PTC3 (RP3) is a fusion oncogene that causes a form of papillary thyroid cancer (PTC). In addition to driving transformation, the constitutively active kinase precociously phosphorylates itself as well as other intracellular proteins, thereby providing tumor-specific targets for the adaptive immune system. PTCs are known to have the ability to escape the immune system driving a dysregulation of the activity of several cell populations involved in the immune response. Indeed we found that mice immunized with RP3+/MHC class II+ cells produce dramatically fewer IFNg-secreting CD4+ T cells compared to mice immunized with RP3-/MHC class II+ counterparts as measured in the spleens. We demonstrated the immunogenicity of RP3 with reactivity in both BALB/c and C57BL/6 mice to RP3/IEd- and RP3/CIITA-expressing cells. Also, we observed immunogenicity of RP3-derived phosphopeptides in ELISpot assays, supporting the hypothesis that the aberrant autophosphorylation of RP3 is a source of tumor-specific immunogenicity. Finally, utilizing a RP3-expressing vaccinia vector for immunization of C57BL/6 mice, we identified peptide sequences that appear to be immunogenic on the basis of unique conformation of the fusion protein that impacts antigen processing. Taken together these results could pave the way for better vaccine approaches without accompanying autoimmunity. Citation Format: Laura Sponton, Gabriela Cosma, Mark Mendonca, Mirella Giovarelli, Laurence Crane Eisenlohr. Identification of tumor-specific antigens associated with RET/PTC3 expression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1294. doi:10.1158/1538-7445.AM2015-1294