Homocitrullinated nucleophosmin (H-NPM1)

Homocitrullinated nucleophosmin is a post-translationally modified form of the nucleophosmin (NPM1) protein, where lysine residues are converted to homocitrulline through a process called carbamylation (Brentville et al., 2020). The native NPM1 protein is a multifunctional nucleolar phosphoprotein essential for ribosome biogenesis, protein chaperoning, and maintaining genomic stability (UniProt P06748). In the tumor microenvironment, metabolic stress and inflammation lead to the accumulation of cyanate, which facilitates the homocitrullination of NPM1, creating neoepitopes that are not typically present in healthy tissues (Brentville et al., 2020). These modified peptides are presented on MHC class II molecules, allowing them to be recognized by the immune system as foreign. Therapeutic strategies, such as the Modi-1 vaccine, target these homocitrullinated neoantigens to stimulate a potent CD4+ T-cell response against various solid tumors, including ovarian and triple-negative breast cancers (Scancell, 2024). This approach aims to overcome immune tolerance to self-antigens by specifically targeting modifications induced by the cellular stress characteristic of malignancy.

Other names

Carbamylated nucleophosminHomocitrullinated NPM1Nucleophosmin 1NPM1

Induction of CD4+ T-cell mediated immune response against modified self-epitopes