Mutant KRAS-derived neoantigen peptide-MHC class I complex (Mutant KRAS-neoantigen-MHC-I)

Mutant KRAS-derived neoantigen peptides presented on MHC class I are tumor-specific antigens formed when mutated KRAS proteins are processed and displayed on the cell surface. KRAS is a GTPase that acts as a molecular switch in signaling pathways like MAPK and PI3K, and its mutations (most commonly G12D, G12V, and G12C) are primary drivers in pancreatic, colorectal, and lung cancers (Simanshu et al., 2017, Cell; Bear et al., 2020, Cancer Cell). These mutant peptides are absent in healthy tissues, making the peptide-MHC (pMHC) complex a highly specific target for immunotherapy (Tran et al., 2016, NEJM). Therapeutic strategies include TCR-engineered T cells (TCR-T) that recognize specific pMHC combinations, such as KRAS G12V on HLA-A*11:01, and therapeutic vaccines like ELI-002 designed to elicit endogenous T-cell responses (Elicio Therapeutics, 2024; Affini-T Therapeutics, 2024). Because these targets are intracellularly derived, they allow the immune system to "see" the internal oncogenic state of the cell. However, challenges include the requirement for specific HLA alleles in patients and the potential for tumor escape through HLA downregulation or loss (Tran et al., 2016, NEJM).

Other names

KRAS mutant pMHCKRAS neoantigen-HLA complexMutant KRAS-HLA-I complexKRAS G12D/G12V/G12C neoantigen

T-cell receptor (TCR) binding and subsequent T-cell mediated lysis of tumor cells expressing the specific mutant KRAS peptide in the context of a compatible HLA molecule.