Mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) G12D peptide presented by Human Leukocyte Antigen (HLA) A*11:01 (KRAS G12D/HLA-A*11:01)

The mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) G12D peptide presented by Human Leukocyte Antigen (HLA) A*11:01 is a tumor-specific neoantigen complex that serves as a high-precision target for cancer immunotherapy (Science, 2016). KRAS is a GTPase involved in signal transduction; the G12D mutation is a frequent driver in pancreatic, colorectal, and lung malignancies (Nature Reviews Cancer, 2022). When this mutated protein is processed by the proteasome, specific peptide fragments are loaded onto the HLA-A*11:01 molecule and displayed on the cell surface (NEJM, 2022). This complex is absent in healthy tissues, making it an ideal target for T-cell receptor (TCR) engineered T-cell therapies and neoantigen vaccines. Therapeutic strategies aim to utilize the specificity of the TCR to recognize this peptide-MHC complex, triggering a cytotoxic immune response against the tumor cells. Clinical development focuses on patients with pancreatic and colorectal cancers who carry both the G12D mutation and the HLA-A*11:01 allele (ClinicalTrials.gov, 2023). This target is particularly significant for populations in East Asia, where the HLA-A*11:01 allele is highly prevalent (Allele Frequency Net Database, 2024).

Other names

KRAS G12D neoantigenHLA-A*11:01-restricted KRAS G12DKRAS G12D peptide-MHC complexKRAS G12D 9-mer/HLA-A*11:01KRAS G12D 10-mer/HLA-A*11:01

Recognition of the mutant peptide-MHC complex by engineered or vaccine-induced T-cell receptors (TCRs) to trigger cytotoxic T-lymphocyte mediated lysis of tumor cells.