HLA-DRB1*07:01–KRAS G12V peptide complex (HLA-DRB1*07:01–KRAS G12V)

The HLA-DRB1*07:01–KRAS G12V peptide complex is a specific molecular assembly consisting of the Human Leukocyte Antigen (HLA) Class II molecule and a mutated peptide fragment from the KRAS protein. KRAS is a GTPase that regulates cell signaling, and the G12V mutation (glycine to valine at position 12) is a frequent oncogenic driver in cancers such as pancreatic, colorectal, and lung adenocarcinoma (PubMed: 27959623). In this complex, the HLA-DRB1*07:01 allele presents the G12V neoantigen on the cell surface, making it a target for recognition by CD4+ T-cell receptors (TCRs). This recognition is vital for the induction of an adaptive immune response against tumor cells. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines like ELI-002, which are designed to stimulate the immune system to selectively destroy KRAS G12V-positive malignant cells (ClinicalTrials.gov: NCT04853017). The complex is considered a "public neoantigen" because it occurs in a significant subset of the patient population sharing this specific HLA allele and mutation. Targeting this complex offers a precision medicine approach to treating KRAS-driven cancers while minimizing damage to healthy cells that lack the mutation. Clinical development focuses on patients who are both HLA-DRB1*07:01 positive and harbor the KRAS G12V mutation in their tumors.

Other names

KRAS G12V/HLA-DRB1*07:01 complexHLA-DRB1*07:01-restricted KRAS G12V neoantigenMHC Class II-KRAS G12V complex

Recognition by specific T-cell receptors (TCRs) on CD4+ T cells, triggering an immune response against cells presenting the KRAS G12V mutation.