Mutant KRAS-derived peptide-HLA class I complex (KRAS-pMHC)

The mutant KRAS-derived peptide presented by HLA class I is a tumor-specific neoantigen complex formed when intracellular mutant KRAS proteins are processed by the proteasome and their resulting peptides are loaded onto Human Leukocyte Antigen (HLA) class I molecules for surface display. KRAS is a small GTPase that, when mutated (most commonly at codon 12), remains in a constitutively active state, driving uncontrolled cell proliferation and survival in various malignancies, including pancreatic, colorectal, and lung cancers. Because these mutations are absent in healthy tissues, the resulting peptide-HLA (pHLA) complexes serve as highly specific targets for immunotherapy. Therapeutic strategies targeting this complex include T-cell receptor-engineered T-cell (TCR-T) therapies, TCR-mimic (TCRm) antibodies, and bispecific T-cell engagers, which are designed to recognize the subtle amino acid differences between mutant and wild-type KRAS peptides. A major challenge in targeting this complex is the requirement for specific HLA matching (e.g., HLA-A*11:01 or HLA-C*08:02) and the potential for tumor immune escape through HLA downregulation or loss of heterozygosity.

Other names

KRAS neoantigen-HLA complexKRAS mutant peptide-MHC complexKRAS-pHLAMutant KRAS-HLA-I complexKRAS G12D/V/C-HLA complex

T-cell receptor (TCR) binding and activation, T-cell mediated cytotoxicity, Immune recruitment via bispecific antibodies