Kirsten rat sarcoma virus proto-oncogene G12V mutant neoantigen (KRAS G12V)

The KRAS G12V mutant neoantigen is a tumor-specific target resulting from a missense mutation in the KRAS gene, where glycine is replaced by valine at codon 12 (p.G12V) [PMID: 30449628]. This mutation impairs the protein's ability to hydrolyze GTP, locking it in a constitutively active state that drives oncogenic signaling through the MAPK and PI3K pathways [PMID: 31549236]. As a neoantigen, the mutated peptide sequence is processed and presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, making it visible to the immune system [PMID: 27959611]. Because this specific sequence is absent in normal tissues, it serves as a highly selective target for immunotherapies such as TCR-engineered T-cell (TCR-T) therapies and cancer vaccines [PMID: 35641551]. Current clinical development focuses on patients with pancreatic, colorectal, and lung cancers, where the G12V mutation is a frequent driver of malignancy and resistance to standard therapies [NCT04146298]. Targeting the neoantigen allows for the precise destruction of cancer cells while sparing healthy cells that express only the wild-type KRAS protein.

Other names

KRAS p.G12VKRAS G12V peptide-MHC complexKirsten rat sarcoma virus oncogene G12VG12V mutant KRAS

T-cell receptor (TCR) mediated recognition of the mutant KRAS G12V peptide presented on specific Major Histocompatibility Complex (MHC) molecules, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of tumor cells.