KRAS G12D mutant peptide-HLA-A*11:01 complex (KRAS G12D/HLA-A*11:01)

The KRAS G12D mutant peptide-HLA-A*11:01 complex is a tumor-specific neoantigen formed when the mutated KRAS protein is processed and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*11:01 (PubMed: 27279826). KRAS G12D is a driver mutation frequently found in high-mortality cancers, including pancreatic (approx. 40%), colorectal, and lung adenocarcinomas (NCI, 2023). Because this specific peptide-MHC complex is absent in healthy tissues, it serves as an ideal target for precision immunotherapy, such as T-cell receptor (TCR) engineered T-cell therapy and cancer vaccines (PubMed: 35653311). The HLA-A*11:01 allele is particularly prevalent in East Asian populations, making this target clinically significant for a large patient demographic (Allele Frequency Net Database). Therapeutic strategies aim to leverage the immune system to recognize this complex, leading to the selective destruction of malignant cells while sparing normal cells. Current clinical efforts, including those by companies like Affini-T Therapeutics and academic institutions, focus on developing high-affinity TCRs that can bind this complex with high specificity (ClinicalTrials.gov: NCT04754100). This target represents a significant advancement in targeting KRAS by shifting the focus from the protein itself to the immune presentation of its mutant fragments.

Other names

KRAS G12D neoantigenHLA-A*11:01-restricted KRAS G12DKRAS G12D-HLA-A11 complexpMHC KRAS G12D/A11:01

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated lysis of tumor cells presenting the KRAS G12D neoantigen (PubMed: 35653311).