This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sebestyen, Z. Articles by Willemsen, R. Search for Related Content PubMed PubMed Citation Articles by Sebestyen, Z. Articles by Willemsen, R.

An Oncolytic Adenovirus Redirected with a Tumor-Specific T-Cell Receptor

¹ Tumor Immunology Group, Unit of Clinical and Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; ² Virus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands; and ³ Got-a-Gene, Götenburg, Sweden

Requests for reprints: Ralph Willemsen, Tumor Immunology Group, Unit of Clinical and Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Groene Hilledijk 301, Rotterdam 3075 EA, the Netherlands. Phone: 31-10-4391574; E-mail: r.a.willemsen{at}erasmusmc.nl.

To improve safety and specificity of oncolytic adenoviruses, we introduced T-cell receptors (TCR) specific for a unique class of truly tumor-specific antigens into the adenoviral fiber protein. The adenoviral fiber knob responsible for attachment to the coxsackie-adenoviral receptor (CAR) on target cells was replaced by a single-chain TCR (scTCR) molecule with specificity for the melanoma-associated cancer-testis antigen MAGE-A1, presented by HLA-A1, and an extrinsic trimerization motif in a replicating Ad5 vector (Ad5.R1-scTCR). The production of the recombinant virus was initiated in a novel producer cell line that expressed an antibody-based hexon-specific receptor (293T-AdR) in the cell membrane. This new production system allowed CAR-independent and target antigen–independent propagation of Ad5.R1-scTCR. Infection with adenovirus bearing the scTCR-based fiber resulted in an efficient killing of target tumor cells. The infection was cell type specific because only HLA-A1⁺/MAGE-A1⁺ melanoma cells were killed, and thus, this retargeting strategy provides a versatile tool for future clinical application. [Cancer Res 2007;67(23):11309–16]

This article has been cited by other articles:

				L. R. Paiva, C. Binny, S. C. Ferreira Jr., and M. L. Martins A Multiscale Mathematical Model for Oncolytic Virotherapy Cancer Res., February 1, 2009; 69(3): 1205 - 1211. [Abstract] [Full Text] [PDF]

				C.-C. Chang, G.-S. Shieh, P. Wu, C.-C. Lin, A.-L. Shiau, and C.-L. Wu Oct-3/4 Expression Reflects Tumor Progression and Regulates Motility of Bladder Cancer Cells Cancer Res., August 1, 2008; 68(15): 6281 - 6291. [Abstract] [Full Text] [PDF]