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

The KRAS G12V neoepitope presented by HLA-A*11:01 is a tumor-specific antigen complex consisting of a mutated fragment of the Kirsten rat sarcoma virus oncogene homolog (KRAS) protein bound to the Human Leukocyte Antigen (HLA) A*11:01 molecule (Wang et al., 2016, Journal of Immunology). KRAS is a small GTPase that acts as a molecular switch in signaling pathways like MAPK and PI3K, which govern cell growth and survival (Prior et al., 2020, Cancer Research). The G12V mutation, involving a glycine-to-valine substitution at codon 12, renders the KRAS protein constitutively active, driving oncogenesis in several major cancers, including pancreatic, colorectal, and lung carcinomas. This specific neoepitope is formed when the mutant protein is processed by the proteasome and the resulting peptide is loaded onto HLA-A*11:01 for presentation on the cell surface. Because this complex is absent from normal, non-mutated cells, it represents an ideal target for precision immunotherapies such as TCR-engineered T-cell (TCR-T) therapy and neoantigen vaccines like ELI-002 (Pant et al., 2024, Nature Medicine). These therapies are designed to bypass central tolerance and induce a potent, mutation-specific immune response. The HLA-A*11:01 restriction is particularly relevant for patient populations in East and Southeast Asia, where this allele is highly prevalent (Gonzalez-Galarza et al., 2020, Nucleic Acids Research).

Other names

KRAS G12V/HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12V neoantigenKRAS G12V neoepitopeMutant KRAS G12V peptide-MHC complexpKRAS G12V/HLA-A*11:01

Recognition of the mutant peptide-HLA complex by engineered T-cell receptors (TCRs) or vaccine-induced T-cells, leading to targeted lysis of tumor cells and cytokine production.