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

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V mutant peptide presented by Human Leukocyte Antigen A*11:01 (HLA-A*11:01) is a tumor-specific neoantigen complex. KRAS is a small GTPase that functions as a critical molecular switch in signaling pathways like MAPK and PI3K, which regulate cell growth and survival (Simanshu et al., 2017, Cell). The G12V mutation involves a glycine-to-valine substitution at position 12, leading to constitutive activation of the protein and driving the progression of various cancers, most notably pancreatic, colorectal, and lung adenocarcinomas (Prior et al., 2020, Cancer Cell). In malignant cells, the mutant KRAS protein is processed into short peptides that are then loaded onto HLA-A*11:01 molecules for presentation on the cell surface (Wang et al., 2016, Cancer Immunology Research). This specific peptide-MHC complex serves as a target for advanced immunotherapies, including T-cell receptor (TCR)-engineered T cells and bispecific antibodies, which are designed to recognize the mutation with high precision (Bear et al., 2022, NEJM). Because the G12V mutation is absent in normal, healthy tissues, targeting this complex provides a highly selective approach to cancer treatment, minimizing off-target effects while inducing potent T-cell mediated cytotoxicity against the tumor.

Other names

KRAS G12V neoantigenHLA-A*11:01-restricted KRAS G12VKRAS G12V peptide-MHC complexKRAS G12V 7-16 peptide/HLA-A*11:01Mutant KRAS G12V presented by HLA-A*11:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and direct lysis of tumor cells.