Mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) neoantigen-MHC complex (Mutant KRAS-pMHC)

Mutant KRAS variants presented as peptides on the Major Histocompatibility Complex (MHC) serve as highly specific tumor neoantigens and represent a major frontier in precision oncology. KRAS is one of the most frequently mutated oncogenes in human cancers, particularly in pancreatic, colorectal, and lung malignancies, where mutations at codons 12, 13, or 61 drive constitutive signaling and cell proliferation (Source: PubMed, PMID: 33009951). Because KRAS is an intracellular protein, its mutant forms are processed by the proteasome into short peptides and displayed on the cell surface by MHC Class I molecules, creating a unique interface for T-cell receptor (TCR) recognition (Source: NEJM, PMID: 27959614). Therapeutic strategies targeting this interface include TCR-engineered T-cell (TCR-T) therapies, which utilize high-affinity receptors to identify specific peptide-HLA combinations, and cancer vaccines designed to prime endogenous T-cell responses against these neoantigens (Source: Nature, PMID: 35197631). These approaches aim to overcome the historical "undruggability" of KRAS by leveraging the immune system's ability to detect intracellular mutations via the cell surface. Current clinical development focuses on specific common mutations like G12D and G12V in the context of prevalent HLA alleles such as HLA-A*11:01 and HLA-C*08:02.

Other names

KRAS neoantigen-HLA complexMutant KRAS-HLA interfaceKRAS G12D-MHC complexKRAS G12V-MHC complexKRAS G12C-MHC complexKRAS mutant peptide-HLA complex

Induction of T-cell mediated cytotoxicity through the specific recognition of mutant KRAS peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of tumor cells.