We have previously shown that anti-tumor T cell response is triggered by anti-CD20-mAb in mice bearing EL4-huCD20 tumor cells, a murine tumor expressing human CD20+ (huCD20) molecule. To define huCD20-derived epitopes that might be targeted by mAb-induced adaptive responses, we have selected different candidate peptides restricted to Kb, Db, and I-Ab, based on in silico prediction and in vitro binding to recombinant MHC molecules. Naive C57Bl/6 mice were then immunized with different mixtures of these peptides and subsequently challenged with EL4-huCD20 tumor cells. A longer survival could be achieved in mice immunized with MHCI and MHCII huCD20-derived peptide mixtures corresponding to various regions of the human CD20 molecule. Then, we defined in the same regions twenty-three huCD20-derived peptides with high in vitro binding to human MHCI and MHCII molecules frequent in Caucasian populations. The use of humanized HLA-DR1/HLA-A2.1 transgenic mice injected with EL4-huCD20 tumor cells and of NIH/3T3 cells expressing accessory and human HLA-DR1 or A2.1 molecules loaded with the candidate peptides made it possible to define 4 MHCI-restricted and 13 MHCII-restricted CD20-derived peptides capable of stimulating IFN-gamma production by specific CD4+ and CD8+ T cells. These findings support further studies on the identification and characterization of CD20-specific T cells in anti-CD20-treated follicular lymphoma patients. The definition of CD20-derived immunogenic epitopes also paves the way for the search of new biomarkers correlating with the clinical outcome of patients.
Citation Format: Sophie Siberil, Benoit Milcent, Quentin Riller, Claire Deligne, Mohamad Hamieh, Olivier Toutirais, Jean-Baptiste Latouche, Jean-Luc Teillaud. Deciphering CD20 immunogenicity to generate protective anti-tumor CD4+ and CD8+ T cells. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B119.
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