Human leukocyte antigen A*11:01-restricted KRAS G12V neoantigen complex (HLA-A*11:01/KRAS-G12V)

The Human leukocyte antigen A*11:01-restricted KRAS G12V neoantigen complex is a peptide-major histocompatibility complex (pMHC) class I molecule that presents a mutated fragment of the KRAS protein on the surface of cancer cells (Wang et al., 2016, PMID: 26437030). KRAS is a GTPase that acts as a molecular switch in cell signaling; the G12V mutation (glycine to valine at codon 12) is a common oncogenic driver in pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer (Prior et al., 2020, PMID: 32103311). In patients with the HLA-A*11:01 allele, which is prevalent in East Asian populations, the G12V mutation creates a unique neoepitope (typically the 10-mer VVVGAVGVGK) that is not found in normal cells (Affini-T Therapeutics, 2024). This high degree of tumor specificity makes the complex an ideal target for T-cell receptor (TCR) based therapies, such as AFNT-211, which are designed to recognize and kill cells expressing this specific pMHC (Affini-T Therapeutics, 2024). Other therapeutic approaches include neoantigen vaccines like ELI-002, which aim to expand endogenous T-cell populations capable of recognizing KRAS mutations presented by various HLA alleles, including HLA-A*11:01 (Elicio Therapeutics, 2024). Because the target is a neoantigen, these therapies generally exhibit a favorable safety profile with minimal on-target, off-tumor toxicity, although challenges such as HLA downregulation and tumor heterogeneity remain (Simanshu et al., 2017, PMID: 28846915). The clinical success of targeting this complex depends on the precise matching of the patient's HLA genotype and the tumor's mutational profile. Ongoing research continues to explore the potential of this target in combination with checkpoint inhibitors to overcome the immunosuppressive tumor microenvironment.

Other names

HLA-A*11:01/KRAS G12VKRAS G12V peptide-HLA-A*11:01 complexKRAS G12V neoantigenHLA-A11:01-KRAS G12V

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