KRAS G12C neoantigen peptide presented by HLA-A*11:01 (KRAS G12C/HLA-A*11:01)

The KRAS G12C neoantigen peptide presented by HLA-A*11:01 is a specific molecular complex formed when the mutated KRAS protein is processed and displayed on the surface of cancer cells. KRAS is a member of the RAS family of small GTPases that regulate cell growth; the G12C mutation (glycine to cysteine at codon 12) is a frequent driver in various malignancies, including lung and colorectal cancers (Simanshu et al., 2017, Cell). In patients carrying the HLA-A*11:01 allele, the mutated peptide fragment is presented by the Major Histocompatibility Complex (MHC) Class I, making it a target for the cellular immune system. This complex is highly tumor-specific because the G12C mutation does not occur in normal, healthy cells, minimizing the risk of on-target, off-tumor toxicity (Bear et al., 2020, Cancer Discovery). Therapeutic strategies targeting this pMHC complex include TCR-engineered T-cells (TCR-T) and peptide vaccines, which aim to induce a robust cytotoxic T-lymphocyte response against the tumor (Wang et al., 2021, Journal of Hematology & Oncology). This target is particularly relevant for precision medicine in populations where the HLA-A*11:01 allele is common, such as in East Asia.

Other names

KRAS G12C-A11:01 complexHLA-A*11:01-restricted KRAS G12C neoantigenKRAS G12C peptide-MHC complexHLA-A*11:01/KRAS(G12C) complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation, cytokine secretion, and direct cytotoxic lysis of the tumor cell.