KRAS G12D mutant decamer peptide presented by HLA-A*11:01 (KRAS G12D/HLA-A*11:01)

The KRAS G12D mutant decamer peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex that serves as a critical target for cancer immunotherapy. KRAS is a small GTPase that acts as a molecular switch in signaling pathways controlling cell growth; the G12D mutation is a common oncogenic driver that locks the protein in an active state, promoting malignancy (Wang et al., 2016, PubMed: 26712445). In patients carrying the HLA-A*11:01 allele, the mutated protein is processed into a 10-amino acid fragment (VVVGADGVGK) and displayed on the cell surface by the Major Histocompatibility Complex (MHC) class I molecule (Sim et al., 2020, PubMed: 32433943). This specific peptide-MHC complex is absent on healthy cells, making it an ideal target for precision therapies such as T-cell receptor (TCR) engineered T-cells and neoantigen vaccines. Therapeutic strategies aim to harness the immune system to recognize this complex, leading to the selective destruction of KRAS G12D-positive tumor cells. This target is particularly relevant for treating pancreatic, colorectal, and lung cancers, where KRAS G12D mutations are highly prevalent and HLA-A*11:01 is a frequent haplotype (ClinicalTrials.gov: NCT03948191).

Other names

KRAS G12D 10-mer/HLA-A*11:01VVVGADGVGK/HLA-A*11:01 complexKRAS G12D neoantigen-MHC complexHLA-A*11:01-restricted KRAS G12D peptide

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like molecules to induce selective lysis of tumor cells expressing the KRAS G12D mutation.