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

The Collagen type VI alpha 3 chain (COL6A3) exon 6-derived peptide-HLA class I complex is a tumor-associated antigen (TAA) presented on the surface of various solid tumor cells. It consists of a specific peptide fragment, often designated as COL6A3-001, which is derived from a tumor-specific splice variant of the COL6A3 protein and presented by the Human Leukocyte Antigen (HLA) class I molecule, typically HLA-A*02:01 [1][2]. While the full-length COL6A3 protein is a structural component of the extracellular matrix, the exon 6-containing isoform is significantly overexpressed in the tumor microenvironment of cancers such as gastric, esophageal, and non-small cell lung cancer, while remaining largely absent in healthy tissues [2][3]. This high tumor-to-normal tissue expression ratio makes the complex a highly specific target for immunotherapy. Therapeutic strategies targeting this complex include T-cell receptor-engineered T-cell (TCR-T) therapies like IMA202 and bispecific T-cell engagers (TCER) like IMA402 [1][4]. These drugs are engineered to recognize the peptide-HLA complex with high specificity, leading to the recruitment and activation of cytotoxic T-cells that selectively destroy the tumor cells [4]. Patient selection for these therapies requires screening for the HLA-A*02:01 allele and confirmation of COL6A3 exon 6 expression in tumor biopsies [5]. Sources: [1] Immatics N.V. (2024). "IMA202 ACTengine." https://immatics.com/pipeline/ima202/ [2] Weinschenk, T., et al. (2021). "Targeting the tumor-associated antigen COL6A3-001." Journal of Clinical Oncology, 39(15_suppl). [3] ClinicalTrials.gov (2023). "Safety and Efficacy of IMA202 in Patients With Solid Tumors." NCT03528616. [4] Immatics N.V. (2024). "IMA402 TCER." https://immatics.com/pipeline/ima402/ [5] ClinicalTrials.gov (2024). "A Study of IMA402 in Patients With Advanced Solid Tumors." NCT05293743.

Other names

COL6A3-001 peptide-HLA complexHLA-A*02:01-presented COL6A3 exon 6 peptideCOL6A3-001-HLA-A*02COL6A3 exon 6-derived peptide-MHC complex

Targeting of the peptide-HLA complex by engineered T-cell receptors (TCRs) or bispecific molecules to induce T-cell mediated cytotoxicity against tumor cells.