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Homocitrullinated alpha-enolase is a post-translationally modified form of the glycolytic enzyme alpha-enolase (ENO1), where lysine residues are converted to homocitrulline through a process known as carbamylation [2, 3]. This modification is typically triggered by environmental stressors such as inflammation, hypoxia, or nutrient deprivation, which are prevalent in the tumor microenvironment [1, 2]. These modified proteins act as neoantigens, which are absent in normal healthy tissues but presented on the surface of stressed or malignant cells [3]. In the field of oncology, homocitrullinated alpha-enolase is a primary target for the Modi-1 therapeutic vaccine, which aims to stimulate a robust CD4+ T-cell response to eliminate tumors [1, 2]. Beyond cancer, this target is significant in the pathogenesis of autoimmune diseases like rheumatoid arthritis, where anti-carbamylated protein (anti-CarP) antibodies serve as important diagnostic and prognostic markers [4]. The therapeutic targeting of these neoantigens provides a strategy to overcome common tumor escape mechanisms, such as the downregulation of MHC class I molecules [2, 3]. Consequently, it represents a promising candidate for selective immunotherapy that exploits the metabolic abnormalities of diseased cells [1, 3].
Induction of a CD4+ T-cell mediated immune response against homocitrullinated neoepitopes presented on MHC class II molecules
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