Adenovirus targeting to HLA-A1/MAGE-A1-positive tumor cells by fusing a single-chain T-cell receptor with minor capsid protein IX
| Autor: | S K van den Hengel, Jort Vellinga, Rob C. Hoeben, Taco Gilles Uil, Emmanuel J. H. J. Wiertz, Ralph A. Willemsen, Steve J. Cramer, Marieke C. Verweij, Danijela Koppers-Lalic, J de Vrij |
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| Přispěvatelé: | Hematology, Neurology, Medical Oncology |
| Rok vydání: | 2008 |
| Předmět: |
Cytotoxicity
Immunologic Male Genetic Vectors Antigen presentation Receptors Antigen T-Cell Human leukocyte antigen Biology medicine.disease_cause Adenoviridae Transduction (genetics) Antigen SDG 3 - Good Health and Well-being Antigens Neoplasm Transduction Genetic Cell Line Tumor Genetics medicine Humans Melanoma Molecular Biology HLA-A1 Antigen Antigen Presentation T-cell receptor Genetic Therapy Flow Cytometry Fusion protein Virology Molecular biology Neoplasm Proteins Capsid Gene Targeting Molecular Medicine Capsid Proteins Genetic Engineering Melanoma-Specific Antigens |
| Zdroj: | Gene Therapy, 15(13), 978-989. Nature Publishing Group |
| ISSN: | 0969-7128 |
| DOI: | 10.1038/gt.2008.26 |
| Popis: | Adenovirus vectors have great potential in cancer gene therapy. Targeting of cancer-testis (CT) antigens, which are specifically presented at the surface of tumor cells by human leukocyte antigen (HLA) class I molecules, is an attractive option. In this study, a single-chain T-cell receptor (scTCR) directed against the CT antigen melanoma-associated antigen ( MAGE)-A1 in complex with the HLA class I molecule of haplotype HLA-A1 is fused with the C terminus of the adenovirus minor capsid protein IX. Propagation of a protein-IX (pIX)-gene-deleted human adenovirus 5 (HAdV-5) vector on cells that constitutively express the pIXscTCR fusion protein yielded viral particles with the pIXscTCR fusion protein incorporated in their capsid. Generated particles specifically transduced melanoma cell lines expressing the HLA-A1/MAGE-A1 target complex with at least 10-fold higher efficiency than control viruses. Whereas loading of HLA-A1-positive cells with MAGE-A1 peptides leads to enhanced transduction of the cells, the efficiency of virus transduction is strongly reduced if the HLA-A1 molecules are not accessible at the target cell. Taken together, these data provide proof of principle that pIXscTCR fusions can be used to target HAdV-5 vectors to tumor cells expressing intracellular CT antigens. |
| Databáze: | OpenAIRE |
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