Mutant KRAS G12V peptide presented by HLA-A*11:01 (KRAS G12V/HLA-A*11:01)

The Mutant KRAS G12V peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex consisting of a mutated fragment of the KRAS protein bound to the Human Leukocyte Antigen (HLA) class I molecule A*11:01. KRAS is a member of the RAS family of GTPases that regulates cell signaling pathways involved in growth and survival; the G12V mutation (glycine to valine at codon 12) results in constitutive activation of the protein, driving oncogenesis in various malignancies such as pancreatic, colorectal, and lung cancers (PubMed: 29950444). This specific peptide-MHC (pMHC) complex is a primary target for immunotherapy because the G12V mutation is somatic and absent in normal tissues, providing a high degree of therapeutic selectivity. Current drug development efforts focus on T-cell receptor (TCR) engineered T-cell therapies, such as AFNT-211, and neoantigen vaccines like ELI-002, which aim to induce a robust cytotoxic T-lymphocyte response against cells displaying this complex (Affini-T Therapeutics; Elicio Therapeutics). The HLA-A*11:01 restriction is particularly significant as this allele is highly prevalent in East and Southeast Asian populations, making it a critical target for precision oncology in these regions (Allele Frequency Net Database). Successful binding of a TCR to this complex initiates an immunological synapse, leading to the directed release of perforins and granzymes that induce apoptosis in the target tumor cell.

Other names

KRAS G12V-HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12V neoantigenKRAS G12V/A*11:01G12V-A11 pMHC

Recognition of the specific peptide-MHC complex by engineered or vaccine-induced T-cell receptors (TCRs), triggering a cytotoxic immune response and subsequent lysis of tumor cells harboring the KRAS G12V mutation.