Kirsten rat sarcoma virus oncogene homolog G12V neoepitope peptide (KRAS G12V neoepitope) (KRAS G12V neoepitope)

The Kirsten rat sarcoma virus oncogene homolog G12V neoepitope peptide (KRAS G12V neoepitope) is a tumor-specific antigen resulting from a point mutation in the KRAS gene, where glycine at position 12 is replaced by valine (Prior et al., 2020). This mutation is a critical driver in various high-mortality cancers, including pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer (Simanshu et al., 2017). As a neoepitope, the mutated peptide is processed and presented on the cell surface by specific Major Histocompatibility Complex (MHC) molecules, such as HLA-A*11:01, making it visible to the immune system (Wang et al., 2021). Because this specific sequence is absent in healthy tissues, it represents an ideal target for precision immunotherapy, offering a high therapeutic index with minimal risk of auto-immunity. Current therapeutic strategies include cancer vaccines like ELI-002 and mRNA-5671, which stimulate the expansion of mutation-specific T cells, as well as adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize the KRAS G12V-HLA complex (Pant et al., 2024). These interventions aim to overcome the immune-silent nature of KRAS-driven tumors by directing a potent, specific T-cell response against the malignant cells.

Other names

KRAS G12V neoantigenKRAS G12V mutant peptideKRAS G12V-derived peptideG12V neoepitope

Induction of a cytotoxic T-lymphocyte response through the recognition of the mutated peptide presented by MHC Class I molecules, leading to selective lysis of tumor cells (Pant et al., 2024; Wang et al., 2021).