KRAS mutant peptide–major histocompatibility complex class I complex (null)

The KRAS mutant peptide–major histocompatibility complex class I complex is a molecular assembly found on the surface of cancer cells that express oncogenic KRAS mutations (most commonly at Glycine 12: G12C, G12V, G12D, etc.)[5]. Mutant KRAS proteins are processed intracellularly, with short peptide fragments derived from the mutant sequence loaded onto MHC class I molecules (or HLA, in humans) and presented on the cell surface. This creates a tumor-specific neoantigen complex which is recognizable by engineered T cell receptors (TCRs), TCR-mimic antibodies, or immunotherapies engineered to bind the mutant peptide–MHC complex[2][4][5][6]. These complexes are the focus of advanced immunotherapeutic strategies for KRAS-driven cancers because they confer specificity for malignant cells, exploit the immune system’s mechanism for distinguishing ‘self’ from ‘non-self,’ and can enable precision T-cell-based therapies or bispecific antibody treatments[1][4][5]. The field is rapidly advancing with efforts to define the structural details of different mutant KRAS peptides in various MHC contexts, test antibody–drug conjugates and bispecific immune cell engagers, and translate them into treatments for otherwise difficult-to-drug KRAS-mutant tumors[1][2][4][5][6].

Other names

KRAS neoantigen–MHC complexKRAS-mutant peptide–HLA complexKRAS mutant neoantigenmutant KRAS peptide–MHCKRAS G12C-G12D-G12V peptide–MHC

Immune cell redirection: TCR-mimic antibodies or bispecific molecules bind the mutant KRAS peptide–MHC complex and recruit or redirect cytotoxic T cells to kill cancer cells presenting the complex[1][4][5]. Direct TCR engagement: Engineered TCRs or TCR-T cells recognize the mutant peptide-MHC on tumor cells and trigger T-cell activation and cytotoxicity[2][6].