KRAS G12V-derived peptide–HLA class I complex (KRAS G12V-HLA)

The KRAS G12V-derived peptide–HLA class I complex is a tumor-specific neoantigen presented on the surface of malignant cells (Nature Communications, 2021). It is formed when the intracellular KRAS protein, carrying a glycine-to-valine mutation at codon 12, is processed into peptide fragments and loaded onto Human Leukocyte Antigen (HLA) class I molecules (Journal of Clinical Investigation, 2024). This complex serves as a unique molecular signature for cancers driven by the KRAS G12V mutation, such as pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer (ESMO Congress, 2025). Because the mutation is absent in healthy tissues, the complex is an ideal target for precision immunotherapies, including T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (NCI Drug Dictionary). These therapies utilize specialized receptors to recognize the peptide-HLA complex and trigger a potent cytotoxic T-cell response against the tumor (Frontiers in Immunology, 2025). Clinical development of these agents often requires patient selection based on both the presence of the KRAS G12V mutation and specific HLA alleles, such as HLA-A*11:01 or HLA-A*03:01 (ClinicalTrials.gov). Targeting this complex offers a way to overcome the "undruggable" nature of the KRAS protein by leveraging the immune system's ability to detect intracellular mutations presented on the cell surface (Nature Communications, 2023).

Other names

KRAS G12V neoantigen-HLA complexKRAS G12V peptide-MHC complexHLA-A*11:01/KRAS G12V complexHLA-A*03:01/KRAS G12V complexKRAS G12V-HLA-A*11:01KRAS G12V-HLA-A*03:01

T-cell receptor (TCR) mediated recognition and cytotoxic T-cell activation