KRAS G12V peptide-HLA-A*03:01 complex (KRAS G12V/HLA-A*03:01)

The KRAS G12V peptide-HLA-A*03:01 complex is a tumor-specific neoantigen target consisting of a mutated fragment of the KRAS protein (specifically the G12V substitution) presented on the cell surface by the Major Histocompatibility Complex (MHC) Class I molecule HLA-A*03:01. KRAS is a small GTPase that functions as a molecular switch in signaling pathways such as MAPK and PI3K, which regulate cell growth and survival. The G12V mutation leads to constitutive activation of the protein, driving oncogenesis in several high-mortality cancers, including pancreatic, colorectal, and non-small cell lung cancers (PubMed: 35653351). Because this specific peptide-MHC complex is a neoantigen—meaning it is derived from a somatic mutation and is not present in healthy tissues—it provides a highly specific target for immunotherapy with minimal risk of systemic toxicity. Current therapeutic strategies include TCR-engineered T-cell (TCR-T) therapies and cancer vaccines like ELI-002, which are designed to stimulate a robust cytotoxic T-lymphocyte response against tumor cells displaying this complex (NCT04853017). Clinical efficacy depends on both the presence of the KRAS G12V mutation and the patient's expression of the HLA-A*03:01 allele.

Other names

KRAS G12V neoantigenHLA-A*03:01-restricted KRAS G12VKRAS G12V 7-16 peptide presented by HLA-A*03:01pMHC KRAS G12V/A*03:01

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity