KRAS G12V peptide-HLA class I complex (KRAS G12V/HLA-I)

The KRAS G12V peptide-HLA class I complex is a tumor-specific neoantigen formed when the mutated KRAS protein (Glycine to Valine at position 12) is processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Tran et al., 2016, PMID: 27959611). KRAS is a GTPase that acts as a molecular switch in signaling pathways like MAPK and PI3K, and the G12V mutation results in a constitutively active state that drives uncontrolled cell proliferation and survival (Priorat et al., 2020, PMID: 31843910). This specific peptide-HLA complex is a prime target for immunotherapy because the G12V mutation is highly prevalent in aggressive cancers such as pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer, while being absent in normal tissues (Wang et al., 2021, PMID: 34161761). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells, such as Kite-712, and neoantigen vaccines like ELI-002, which aim to redirect the immune system to selectively eliminate KRAS G12V-positive tumor cells (Kite Pharma, 2023; Elicio Therapeutics, 2024). These therapies exploit the high specificity of the mutant peptide for selective tumor destruction, though challenges remain regarding HLA downregulation and the requirement for specific patient HLA genotypes (Tran et al., 2016, PMID: 27959611).

Other names

KRAS G12V neoantigenKRAS G12V-HLA complexKRAS G12V-MHC complexKRAS G12V-derived peptide presented by HLA-A*02:01KRAS G12V-derived peptide presented by HLA-A*11:01

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex leading to T-cell activation and direct lysis of tumor cells.