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Collagen type VI alpha 3 chain (COL6A3) exon 6-derived peptide presented on HLA-A*02 (COL6A3-002)

Target
COL6A3-002
Molecular classification
Peptide-MHC complex, Tumor-associated antigen
01

Overview

The target is a specific peptide-MHC complex comprising a peptide derived from exon 6 of the Collagen type VI alpha 3 chain (COL6A3) presented on the Human Leukocyte Antigen (HLA)-A*02 allele (Immatics, 2024). COL6A3 is an extracellular matrix protein, but the specific isoform containing exon 6 is highly overexpressed in the stroma and tumor cells of multiple solid tumors, including pancreatic, gastric, and esophageal cancers (ClinicalTrials.gov, NCT03450156). In contrast, this isoform shows minimal to no expression in healthy tissues, providing a wide therapeutic window for oncology treatments (PubMed, PMID: 31515461). This complex is targeted by advanced immunotherapies such as TCR-engineered T-cells (TCR-T) and T-cell engaging bispecifics (TCERs). These therapies, such as IMA202 and IMA402, utilize high-affinity T-cell receptors to recognize the COL6A3-002 peptide, leading to the directed destruction of malignant cells (Immatics, 2023). Patient selection for these therapies typically requires confirmation of the HLA-A*02 genotype and quantitative assessment of COL6A3 exon 6 mRNA expression in tumor biopsies.

Other names
COL6A3-002HLA-A*02-restricted COL6A3 peptideCOL6A3 exon 6 peptide-HLA complexIMA202 targetIMA402 target
02

Mechanism of action

T-cell receptor (TCR)-mediated recognition of the peptide-HLA complex, inducing cytotoxic T-cell activation and tumor cell lysis.

03

Biological functions

Antigen presentationImmune response
04

Disease associations

Gastric cancerPancreatic cancerEsophageal cancerColorectal cancerNon-small cell lung cancerOvarian cancerBreast cancer
05

Safety considerations

On-target off-tumor toxicityCytokine release syndromeImmune effector cell-associated neurotoxicity syndrome (ICANS)
06

Interacting drugs

IMA202

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 positivityCOL6A3 exon 6 mRNA expression levels

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