Kirsten rat sarcoma viral oncogene homolog G12V mutant peptide–HLA-A*11 complex (KRAS G12V–HLA-A*11 complex)

The **Kirsten rat sarcoma viral oncogene homolog G12V mutant peptide–HLA-A*11 complex** is a molecular structure formed when a short fragment (peptide) derived from the mutated form of the human **KRAS** protein—specifically with a glycine-to-valine substitution at position 12 (**Gly12Val**, or **G12V**)—is presented on the surface of cancer cells by the major histocompatibility complex class I molecule **HLA-A*11**. The wild-type and especially mutated forms of *KRAS*, including *G12V*, are among the most common driver mutations in solid tumors such as colorectal, lung, and pancreatic cancers[1][2][3]. This particular combination creates a "neoantigen" that can be specifically recognized by cytotoxic CD8+ T lymphocytes if their receptors are engineered or naturally able to bind it. As such, it represents an important therapeutic target for personalized cancer immunotherapy approaches—including adoptive cell transfer using engineered TCR-T cells or development of therapeutic vaccines—aimed at selectively eliminating tumor cells harboring both the *KRAS G12V mutation* and expressing *HLA-A*11*. The underlying biology involves loss-of-function in intrinsic GTPase activity due to mutation at codon 12 in *KRAS*, resulting in constitutive activation that drives uncontrolled proliferation and oncogenesis[1][4]. Presentation via HLA molecules enables immune system targeting but only if both genetic features (*KRAS-Gly^12^Val*, HLA type A*11) are present. This makes it highly specific but also limits its applicability based on patient genetics. No small-molecule drugs directly interact with this MHC-peptide structure; instead, research focuses on leveraging its unique presence for targeted immune-based therapies.

Other names

KRAS G12V mutant peptide–HLA-A*11 complexKRAS G12V neoantigen–HLA-A*11Mutant KRAS (G12V) peptide presented by HLA-A*11KRAS Gly12Val-HLA-A*11 complex

For therapies targeting this molecule, the mechanism would involve recognition of the mutant peptide-HLA complex by engineered T cell receptors or antibodies leading to targeted killing of tumor cells presenting this epitope.