Homocitrullinated peptides from nucleophosmin, α-enolase, β-catenin, and heat shock protein 60 (HSP-60) (Hcit-peptides (NPM1/ENO1/CTNNB1/HSPD1))

This target consists of a set of homocitrullinated (carbamylated) peptides derived from four intracellular proteins: nucleophosmin (NPM1), α-enolase (ENO1), β-catenin (CTNNB1), and heat shock protein 60 (HSPD1). Homocitrullination is a stress-induced post-translational modification (siPTM) where lysine residues are converted to homocitrulline by cyanate, a process often catalyzed by myeloperoxidase (MPO) in the inflammatory tumor microenvironment (TME). These modified peptides act as neoantigens that are presented on MHC class II molecules, bypassing central tolerance and allowing for the activation of potent, cytotoxic CD4+ T-cell responses. This target set is being explored primarily for cancer immunotherapy, specifically in the development of therapeutic vaccines like Scancell's Moditope platform (e.g., Modi-2 and Modi-3). By targeting these siPTMs, the immune system can selectively destroy tumor cells that express these modified proteins under stress, while sparing healthy tissues where such modifications are absent or not presented. Research has shown that these epitopes can induce effective anti-tumor immunity in various solid tumor models, including lung, colorectal, and breast cancers, particularly those with an immunosuppressive microenvironment rich in MPO-producing myeloid-derived suppressor cells (MDSCs).

Other names

Carbamylated peptidesHomocitrullinated antigensStress-induced post-translational modificationssiPTMsHcit-NPM1Hcit-ENO1Hcit-CTNNB1Hcit-HSPD1

Induction of cytotoxic CD4+ T-cell responses against homocitrullinated neoepitopes presented on MHC class II molecules.