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

The Collagen type VI alpha 3 chain (COL6A3) exon 6-derived peptide-HLA complex is a tumor-associated antigen (TAA) target used in cancer immunotherapy. It consists of a specific peptide fragment, often designated as COL6A3-002, which is derived from the protein product of an alternatively spliced variant of the COL6A3 gene and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, typically HLA-A*02:01 (Source: Immatics, 2023). While the standard COL6A3 protein is a common extracellular matrix component, the exon 6-containing isoform is highly enriched in the tumor microenvironment and tumor cells of various solid tumors, including pancreatic and colorectal cancers, but is minimally expressed in normal tissues (Source: PubMed, PMID: 30135175). This specific expression profile allows for the development of T-cell receptor (TCR)-based therapies, such as IMA202, which are engineered to selectively bind this complex and trigger a cytotoxic T-cell response against the malignancy (Source: ClinicalTrials.gov, NCT03450156). Therapeutic strategies targeting this complex aim to overcome the immunosuppressive tumor microenvironment by providing high-affinity recognition of a target that is otherwise invisible to the standard immune repertoire. Monitoring for HLA-A*02:01 status and tumor-specific splicing of COL6A3 is essential for patient selection in clinical trials.

Other names

COL6A3-002 peptide-HLA complexCOL6A3 exon 6-derived peptide-MHC complexTumor-associated antigen COL6A3-002COL6A3-002 peptide-HLA-A*02 complex

T-cell receptor (TCR) mediated recognition and cytotoxic destruction of cells presenting the peptide-HLA complex