Mutant RAS neoantigen-Major Histocompatibility Complex (Mutant RAS-MHC)

Mutant RAS neoantigen-Major Histocompatibility Complex (MHC) refers to the cell-surface presentation of peptide fragments derived from mutated RAS proteins (primarily KRAS, NRAS, or HRAS) bound to MHC molecules. In malignant cells, somatic mutations such as KRAS G12D, G12V, or G12C result in the production of "non-self" proteins that are processed by the proteasome and displayed as neoantigens. These complexes are critical targets for modern immunotherapy because they are absent in healthy tissues, providing a high degree of tumor specificity. Therapeutic interventions targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, neoantigen vaccines, and bispecific T-cell engagers designed to recognize the unique spatial configuration of the mutant peptide within the MHC groove. Because RAS mutations are prevalent in highly aggressive cancers like pancreatic and colorectal carcinomas, these complexes represent a major focus for overcoming the limitations of traditional small-molecule RAS inhibitors. However, the efficacy of these therapies is often constrained by the diversity of human leukocyte antigen (HLA) alleles and the potential for tumors to escape immune detection by downregulating MHC expression.

Other names

Mutant RAS peptide-HLA complexRAS neoantigen-pHLAKRAS neoantigen-MHCMutant RAS-HLA complex

Recognition of specific mutant peptide-MHC complexes by T-cell receptors (TCRs) or TCR-like molecules to induce targeted cell death via cytotoxic T-lymphocyte activation.