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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2272-2280. Prepublished online as a Blood First Edition Paper on May 25, 2004; DOI 10.1182/blood-2003-11-3803. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3803v1 104/8/2272    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yotnda, P. Articles by Brenner, M. Search for Related Content PubMed PubMed Citation Articles by Yotnda, P. Articles by Brenner, M. Related Collections Immunobiology Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Targeted delivery of adenoviral vectors by cytotoxic T cells Patricia Yotnda, Barbara Savoldo, Nicolas Charlet-Berguerand, Cliona Rooney, and Malcolm Brenner From the Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Methodist Hospital, Houston, TX; and the Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch, France. Effective targeting of vectors to tumor cells that have metastasized to multiple different tissue sites remains a major challenge for gene therapy. Tumor-specific cytotoxic T lymphocytes (CTLs) have been shown in animal models and in humans to be able to cross tissue barriers and traffic to tumor cells. However, their capacity to eliminate malignancy has been limited by tumor immune evasion strategies. We now use a model of Epstein-Barr virus–mediated malignancy to show that human CTLs themselves may be modified to release therapeutic vectors following engagement of their antigen-specific receptors and that these vectors will effectively transduce and destroy tumor targets. We generated EBV-specific CTLs that were transgenic for the adenoviral E1 gene under the control of the cell activation-dependent CD40 ligand (CD40L) promoter. Following transduction with E1-deficient adenoviral vectors, these CTLs produced infectious virus when exposed to HLA-matched EBV-expressing targets, but not on exposure to major histocompatibility complex (MHC)–mismatched or otherwise irrelevant cells. This approach provides a means of delivering oncolytic/therapeutic vectors not only to locally accessible macroscopic tumors as is presently the case, but also to disseminated metastatic disease, while avoiding the risks associated with systemic administration of large doses of adenoviral vectors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Komarova, Y. Kawakami, M. A. Stoff-Khalili, D. T. Curiel, and L. Pereboeva Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol. Cancer Ther., March 1, 2006; 5(3): 755 - 766. [Abstract] [Full Text] [PDF]

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