Human leukocyte antigen A*11:01:Kirsten rat sarcoma viral oncogene homolog G12V neoepitope peptide complex (HLA-A*11:01:KRAS G12V)

The Human leukocyte antigen A*11:01:Kirsten rat sarcoma viral oncogene homolog G12V neoepitope peptide complex is a specific peptide-major histocompatibility complex (pMHC) that presents a mutated fragment of the KRAS protein on the surface of cancer cells. KRAS is a key signaling protein, and its G12V mutation is a prevalent driver in aggressive malignancies such as pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer, often associated with poor prognosis and resistance to standard therapies (NIH, 2023). In individuals with the HLA-A*11:01 allele, the mutated KRAS peptide (typically the 9-mer VVGAVGVGK or 10-mer VVVGAVGVGK) is displayed for recognition by the immune system (Myrio Tx, 2025). This complex serves as a "public neoantigen," providing a highly specific target for adoptive cell therapies such as TCR-engineered T-cells (e.g., NW-301V) and bispecific T-cell engagers (TCEs) (ESMO, 2025; Affini-T, 2024). These therapeutic approaches aim to redirect T-cell cytotoxicity specifically toward tumor cells while sparing healthy tissues. However, a critical safety concern is the potential for off-target cross-reactivity with similar self-peptides, such as those from the RAB7B protein, which requires rigorous screening of TCR candidates (NIH, 2025). Additionally, the low density of these complexes on the tumor surface and the potential for HLA downregulation present ongoing challenges for achieving durable clinical responses (JCI, 2025).

Other names

KRAS G12V/HLA-A*11:01 complexHLA-A11:01-KRAS-G12VKRAS G12V neoantigen-HLA complexpMHC complexHLA-A*11:01:KRAS G12V 9-mer complexHLA-A*11:01:KRAS G12V 10-mer complex

The complex acts as a specific ligand for engineered T-cell receptors (TCRs) or TCR-like antibodies. Upon binding, it facilitates the formation of an immunological synapse between the effector T-cell and the tumor cell, leading to T-cell activation, secretion of pro-inflammatory cytokines such as interferon-gamma and interleukin-2, and the release of cytotoxic molecules like perforin and granzymes, which induce tumor cell apoptosis.