KRAS G12D-derived peptide presented by MHC class I (KRAS G12D/MHC-I)

The KRAS G12D-derived peptide presented by MHC class I is a prominent neoantigen target in oncology, particularly for cancers with high KRAS mutation rates such as pancreatic, colorectal, and lung adenocarcinomas. The KRAS protein is a GTPase that normally regulates cell growth signaling; however, the G12D mutation results in a constitutively active state that drives oncogenesis. When the mutant KRAS G12D protein is processed by the cellular proteasome, the resulting mutant peptides are loaded onto Major Histocompatibility Complex (MHC) Class I molecules and displayed on the cell surface for surveillance by CD8+ T cells. Because this specific peptide sequence is absent in healthy cells, it serves as a highly specific target for immunotherapy. Current therapeutic strategies include TCR-engineered T-cell (TCR-T) therapies, which utilize receptors specifically cloned to recognize the G12D peptide in the context of specific HLA alleles like HLA-A*11:01 or HLA-C*08:02. Additionally, neoantigen vaccines and bispecific T-cell engagers are being developed to enhance the immune system's ability to selectively eliminate KRAS G12D-positive tumor cells while minimizing damage to normal tissues.

Other names

KRAS G12D neoantigenKRAS G12D peptide-HLA complexKRAS G12D pHLAKRAS G12D/HLA-A*11:01KRAS G12D/HLA-C*08:02Mutant KRAS G12D antigen

Targeting of the specific mutant peptide-MHC complex by T-cell receptors (TCRs), TCR-like antibodies, or vaccines to induce T-cell mediated lysis of tumor cells.