Mutant RAS neoantigen epitopes presented on MHC molecules (mRAS-MHC)

Mutant RAS neoantigen epitopes presented on MHC molecules are highly specific tumor antigens derived from oncogenic mutations in the RAS GTPase family, particularly KRAS. These mutations, which occur at hotspots such as G12, G13, and Q61, create unique peptide sequences that are processed intracellularly and displayed on the cell surface by Major Histocompatibility Complex (MHC) Class I or II molecules [3, 12]. Because these neoepitopes are absent in healthy tissues, they serve as ideal targets for precision immunotherapies, including T-cell receptor-engineered T-cell (TCR-T) therapies, bispecific T-cell engagers, and cancer vaccines [11, 17]. A novel therapeutic approach also involves the use of covalent RAS inhibitors to create drug-modified (haptenated) neoantigens that can be targeted by specialized TCR-mimic antibodies [1, 9]. Despite their high specificity, the clinical utility of these targets is often challenged by low antigen density on the tumor surface and the potential for immune escape through MHC downregulation [5, 8].

Other names

Mutant RAS peptide-MHC complexKRAS neoantigen-HLA complexRAS-derived neoepitopesmRAS-pMHCMutant RAS-HLA complex

T-cell receptor (TCR) mediated recognition, redirected T-cell lysis, and induction of cytotoxic T-lymphocyte (CTL) responses against cells presenting mutant RAS peptides.