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Homocitrullinated vimentin peptide is a post-translationally modified form of the intermediate filament protein vimentin, where lysine residues are converted to homocitrulline through carbamylation (Brentville et al., 2020, Cancer Research; Mydel et al., 2010, Journal of Immunology). This modification typically occurs under conditions of inflammation or metabolic stress, such as high levels of cyanate, making it a stress-induced post-translational modification (siPTM) (Brentville et al., 2020; Shi et al., 2011, PNAS). In autoimmune diseases like rheumatoid arthritis, homocitrullinated vimentin acts as a potent autoantigen, leading to the production of anti-carbamylated protein (anti-CarbP) antibodies which serve as diagnostic biomarkers (Shi et al., 2011). More recently, it has been identified as a neoantigen in various cancers, including melanoma and triple-negative breast cancer, where it is presented on the cell surface by MHC class II molecules (Scancell Holdings plc, 2023, Moditope Platform). Therapeutic strategies, such as the Modi-1 vaccine, aim to stimulate CD4+ T-cell responses against these modified peptides to selectively destroy tumor cells (Cook et al., 2018, Frontiers in Immunology). Because the modification is associated with the cellular stress environment of tumors, it provides a mechanism for specific immune targeting while potentially sparing healthy, non-stressed tissues (Brentville et al., 2020; Cook et al., 2018).
Induction of CD4+ T-cell mediated immune response against stress-induced post-translational modifications (siPTMs)
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