Kirsten rat sarcoma virus oncogene homolog G12V peptide-Human Leukocyte Antigen-A*11:01 complex (KRAS G12V/HLA-A*11:01)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V peptide-Human Leukocyte Antigen (HLA)-A*11:01 complex is a tumor-specific neoantigen target formed when the mutated KRAS protein is processed and its G12V-containing peptide is presented on the cell surface by the HLA-A*11:01 allele (Wang et al., 2016, Cancer Immunol Res). KRAS is a small GTPase that regulates signal transduction pathways for cell growth; the G12V mutation impairs GTP hydrolysis, leading to constitutive activation and driving oncogenesis in pancreatic, colorectal, and lung cancers (Simanshu et al., 2017, Cell). Because this peptide-MHC (pMHC) complex is absent on healthy cells, it serves as a highly specific target for cancer immunotherapies, including TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines (Bear et al., 2020, J Clin Invest). Drugs such as AFNT-211 are being developed to specifically recognize this complex, aiming to provide a precision medicine approach for patients carrying both the G12V mutation and the HLA-A*11:01 genotype (Affini-T Therapeutics, 2023). These therapies aim to induce a robust cytotoxic T lymphocyte response to eliminate tumor cells while minimizing off-target toxicity (Pant et al., 2024, Nature Medicine).

Other names

KRAS G12V-HLA-A*11:01KRAS G12V neoantigenHLA-A*11:01-restricted KRAS G12V peptidepMHC KRAS G12V/A11:01Kirsten rat sarcoma virus oncogene homolog G12V-HLA-A*11:01 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, which triggers the activation of cytotoxic T lymphocytes (CTLs) and subsequent lysis of the target tumor cells.