Mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) neoantigen peptide-Major Histocompatibility Complex (MHC) complex (Mutant KRAS-pMHC)

The mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) neoantigen peptide-Major Histocompatibility Complex (MHC) complex is a critical target in cancer immunotherapy, representing a tumor-specific marker formed by the intracellular processing of mutated KRAS proteins. KRAS is one of the most frequently mutated genes in human malignancies, particularly in pancreatic, colorectal, and lung cancers, where mutations like G12D, G12V, and G12C drive oncogenesis (Simanshu et al., 2017, Cell). These mutations result in unique amino acid sequences that are not present in normal cells; when these mutant peptides are loaded onto MHC Class I molecules and displayed on the cell surface, they become visible to the adaptive immune system (Leidner et al., 2022, NEJM). Therapeutic interventions such as TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines are designed to exploit this visibility by providing or eliciting T-cells that specifically recognize the mutant KRAS-pMHC complex. Because the target is derived from a driver mutation essential for tumor survival, it is less prone to antigen loss than non-essential antigens, although tumors may still escape via MHC downregulation (Blair et al., 2021, Cancer Discovery). Current clinical efforts focus on matching specific KRAS mutations with the patient's HLA type to ensure effective presentation and recognition (Pant et al., 2024, Nature Medicine). This target offers a high degree of precision, as the neoantigen is entirely absent from healthy tissue, theoretically providing a wide therapeutic window.

Other names

KRAS neoantigen-HLA complexMutant KRAS peptide-MHCKRAS G12D/G12V/G12C neoantigen complexKRAS-derived neoepitope-MHC

T-cell receptor (TCR) mediated recognition of the mutant peptide-MHC complex, triggering cytotoxic T-lymphocyte (CTL) activation and subsequent apoptosis of the target cancer cell.