Mutant Kirsten rat sarcoma virus oncogene homolog-derived peptide epitopes presented on Major Histocompatibility Complex molecules (Mutant KRAS-MHC complex)

Mutant KRAS-derived peptide epitopes presented on Major Histocompatibility Complex (MHC) molecules are a class of tumor-specific neoantigens that arise from somatic mutations in the KRAS oncogene (Prior et al., 2020; PMID: 32139493). KRAS is frequently mutated in high-mortality cancers, including pancreatic, colorectal, and lung adenocarcinomas, with common substitutions occurring at positions G12, G13, and Q61. These mutations result in the production of "non-self" peptides that are processed and displayed on the cell surface by MHC class I or II molecules (Bear et al., 2021; PMID: 33859187). Because these specific peptide-MHC complexes are absent in normal tissues, they provide a unique window for therapeutic intervention using T-cell receptor (TCR) engineered T-cells, bispecific antibodies, and cancer vaccines (Leidner et al., 2022; PMID: 35648549). Targeting these epitopes aims to harness the specificity of the adaptive immune system to selectively destroy KRAS-mutant tumor cells while minimizing damage to healthy cells expressing wild-type KRAS. However, therapeutic success depends on the patient's specific HLA genotype and the stability of the peptide-MHC interaction (Wang et al., 2016; PMID: 27760344).

Other names

KRAS neoantigensKRAS mutant peptides on HLAKRAS-HLA complexesMutant KRAS-MHC class I complexKRAS-derived neoepitopes

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity