Abstract B104: Post-translationally modified homocitrulline induced by MDSCs can be an effective antitumor target for CD4 T-cells

Post-translational modifications such as citrullination and phosphorylation have been shown to provide novel target for cancer vaccines. Epitopes from modified proteins allow the generation of cytotoxic CD4 cells capable of targeting tumor. In this study we show that homocitrulline, an amino acid produced when lysine is post translationally modified by the process of carbamylation, can be a target for effective tumor immunity. Homocitrullinated epitopes from the cytoskeletal protein vimentin and the glycolytic enzyme aldolase were selected based upon MHC-II binding algorithms. Immunization of HLA transgenic mice with three homocitrullinated peptides, one from vimentin and two from aldolase A, induced potent IFNγ responses restricted via HLA-DR4, DR1 or DP4. Responses are specific to the homocitrullinated peptides and did not cross react with unmodified peptides. The responses have been characterized as CD4-mediated, Th1-type responses with minimal IL-10 or IL-17 production. In humans, we have also shown that healthy donors and cancer patients both have a CD4 T-cell repertoire recognizing these homocitrullinated peptides. In B16 melanoma tumor models, vaccination with homocitrullinated peptides increases survival in transgenic HLA-DR4 (survival 70%, p=0.0042), HHDII/DR1 (survival 50%, p Citation Format: Katherine W. Cook, Wei Xue, Peter Symonds, Mohamed Gijon, Sabaria Shah, Suha Atabani, Poonam Vaghela, Ruhul Choudhury, Rachael L. Metheringham, Ian Daniels, Victoria Brentville, Lindy Durrant. Post-translationally modified homocitrulline induced by MDSCs can be an effective antitumor target for CD4 T-cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B104.