Abstract 3977: Mark cancer cells for CTL attack through coating with viral antigenic peptides.

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Abstract Selectively coating tumor cells with foreign antigenic peptide may render coated tumor susceptible to immune recognition and elimination, thereby bypassing immune tolerance. Here we create a therapeutic chimeric protein comprised of a tumor-homing module fused to a functional cargo domain containing foreign antigenic peptide. The tumor-homing module is comprised of mesothelin-specific single chain variable fragment that specifically binds to mesothelin, commonly overexpressed in ovarian tumors. The functional cargo domain is comprised of Fc (IgG2a) protein and MHC class I-restricted foreign CD8+ T cell epitope flanked by furin cleavage sites, which can be recognized by furin highly expressed in the tumor microenvironment. We show that our therapeutic protein specifically loaded antigenic epitope onto MHC class I of bound tumor cells, rendering them susceptible to antigen-specific CD8+ T cell-mediated killing for potent antitumor effects in vitro and in vivo. Our findings have important implications for bypassing immune tolerance to enhance cancer immunotherapy.Selectively coating tumor cells with foreign antigenic peptide may render coated tumor susceptible to immune recognition and elimination, thereby bypassing immune tolerance. Here we create a therapeutic chimeric protein comprised of a tumor-homing module fused to a functional cargo domain containing foreign antigenic peptide. The tumor-homing module is comprised of mesothelin-specific single chain variable fragment that specifically binds to mesothelin, commonly overexpressed in ovarian tumors. The functional cargo domain is comprised of Fc (IgG2a) protein and MHC class I-restricted foreign CD8+ T cell epitope flanked by furin cleavage sites, which can be recognized by furin highly expressed in the tumor microenvironment. We show that our therapeutic protein specifically loaded antigenic epitope onto MHC class I of bound tumor cells, rendering them susceptible to antigen-specific CD8+ T cell-mediated killing for potent antitumor effects in vitro and in vivo. Our findings have important implications for bypassing immune tolerance to enhance cancer immunotherapy. Citation Format: Chien-Fu Hung. Mark cancer cells for CTL attack through coating with viral antigenic peptides. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3977. doi:10.1158/1538-7445.AM2013-3977