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

The KRAS G12D decamer peptide presented by HLA-A*11:01 is a specific neoantigen complex consisting of a 10-amino acid fragment (VVVGADGVGK) of the mutated KRAS protein bound to the MHC Class I molecule HLA-A*11:01 (Wang et al., 2022, PMID: 35653311). KRAS G12D is a highly prevalent oncogenic driver mutation, particularly in pancreatic, colorectal, and lung cancers, where it promotes constitutive signaling for cell proliferation and survival (Prior et al., 2020, PMID: 32103171). This peptide-MHC complex is a primary target for T-cell based immunotherapies because it is uniquely expressed on the surface of tumor cells, providing a high degree of specificity. Therapeutic strategies such as TCR-engineered T-cell (TCR-T) therapies, including AFNT-211, are designed to recognize this complex and trigger a potent cytotoxic immune response against the malignancy (Affini-T Therapeutics, 2023). Because the target is a neoantigen, it offers a significant therapeutic window with minimal risk of off-tumor toxicity to healthy tissues expressing wild-type KRAS. However, clinical utility is restricted to patients who both harbor the G12D mutation and possess the HLA-A*11:01 allele, which is notably frequent in East Asian populations.

Other names

KRAS G12D 10-mer/HLA-A*11:01KRAS G12D VVVGADGVGK peptide-HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12D neoantigenKRAS G12D decamer/MHC Class I complex

The mechanism involves the high-affinity binding of an engineered or endogenous T-cell receptor (TCR) to the KRAS G12D/HLA-A*11:01 complex, which induces T-cell activation, secretion of cytotoxic granules such as perforin and granzyme, and subsequent apoptosis of the target cancer cell (Tran et al., 2016, PMID: 27929009).