Kirsten rat sarcoma virus oncogene homolog G12V mutant neoantigen (KRAS G12V) (KRAS G12V)

KRAS G12V mutant neoantigens are tumor-specific peptides resulting from a somatic point mutation in the KRAS gene, where glycine is replaced by valine at codon 12 (PubMed: 31578134). These neoantigens are processed intracellularly and presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, such as HLA-A*11:01, making them visible to the immune system (Nature: 10.1038/nature14404). Because these sequences are entirely absent in healthy tissues, they represent highly specific targets for immunotherapy with a low risk of off-target toxicity. The G12V mutation is a major oncogenic driver in several cancers, including approximately 30% of pancreatic cancers and 10% of colorectal cancers (NIH: PDQ Cancer Information). Therapeutic approaches targeting these neoantigens include cancer vaccines like ELI-002 and mRNA-5671, as well as adoptive TCR-T cell therapies (Nature Medicine: 10.1038/s41591-023-02760-3). These treatments aim to stimulate or provide T-cells that specifically recognize and kill tumor cells harboring the G12V mutation. However, clinical success depends on the patient's HLA type and the tumor's ability to maintain antigen presentation.

Other names

KRAS G12VKRAS p.G12V neoantigenKRAS-G12V peptide-HLA complexMutant KRAS G12V antigen

T-cell receptor (TCR) mediated recognition of the KRAS G12V peptide-MHC complex, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of tumor cells.