Collagen type VI alpha 3 chain exon 6 peptide-HLA complex (COL6A3-E6-HLA)

The Collagen type VI alpha 3 chain (COL6A3) exon 6 peptide-HLA complex is a tumor-associated antigen target primarily utilized in the development of cancer immunotherapies, such as TCR-engineered T-cell therapies. This target arises from the alternative splicing of the COL6A3 gene, where exon 6 is frequently overexpressed in the tumor stroma and cancer cells of various solid tumors, including pancreatic and colorectal cancers, while remaining largely absent in healthy adult tissues (Immatics, 2023; PubMed: 30232145). The specific peptide derived from this splice variant, often designated as COL6A3-002, is processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, most commonly the HLA-A*02:01 allele. Therapeutic strategies like IMA202 are designed to specifically recognize this peptide-MHC complex to induce a targeted cytotoxic immune response against malignant cells (ClinicalTrials.gov: NCT03486873). By focusing on a peptide derived from a tumor-specific splicing event rather than the wild-type protein, these therapies aim to achieve high tumor specificity and minimize off-target effects on the normal extracellular matrix. Patient selection for these therapies typically requires screening for both the specific HLA genotype and the presence of the COL6A3 exon 6 biomarker in tumor biopsies.

Other names

COL6A3-002 peptide-HLA complexCOL6A3 exon 6 variant peptide-MHCTumor-associated antigen COL6A3-002COL6A3-002-HLA-A*02

T-cell receptor (TCR) binding to the peptide-HLA complex on the surface of tumor cells, which triggers T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and subsequent lysis of the target malignant cell.