Collagen type VI alpha 3 chain exon 6 peptide–HLA-A*02:01 complex (COL6A3-001–HLA-A*02:01)

The Collagen type VI alpha 3 chain (COL6A3) exon 6 peptide–HLA-A*02:01 complex is a tumor-associated antigen (TAA) target specifically designed for cancer immunotherapy. It comprises a peptide fragment (FLLDGSANV) derived from the alternatively spliced exon 6 of the COL6A3 gene, which is presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01 (Immatics, 2024). While COL6A3 is a structural protein of the extracellular matrix, the exon 6-containing isoform is predominantly expressed in the stroma and tumor cells of various solid tumors, such as pancreatic, colorectal, and ovarian cancers, while remaining largely absent in healthy tissues (PubMed, PMID: 32661153). This high tumor-specificity allows for the development of precision medicines, including T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific T-cell engaging receptors (TCERs). Drugs like IMA202 and IMA402 are engineered to recognize this specific pMHC complex, triggering a potent T-cell mediated immune response against the cancer cells (ClinicalTrials.gov, NCT03505190). Clinical application of these therapies requires patients to be HLA-A*02:01 positive and demonstrate sufficient expression of the COL6A3 exon 6 biomarker.

Other names

COL6A3-001 peptide-MHC complexHLA-A*02:01/COL6A3-001COL6A3 exon 6-derived peptide-HLA-A*02:01 complexFLLDGSANV-HLA-A*02:01 complex

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte activation against cells presenting the peptide-MHC complex.