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Journal of Virology, May 2008, p. 4680-4684, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.00232-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

High-Capacity Adenovirus Vector-Mediated Anti-Glioma Gene Therapy in the Presence of Systemic Antiadenovirus Immunity{triangledown}

Gwendalyn D. King,1 A. K. M. Ghulam Muhammad,1 Weidong Xiong,1 Kurt M. Kroeger,1 Mariana Puntel,1 Daniel Larocque,1 Donna Palmer,2 Philip Ng,2 Pedro R. Lowenstein,1,3,4 and Maria G. Castro1,3,4*

Board of Governors’ Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Department of Medicine and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 8700 Beverly Blvd., Davis Bldg., Rm. 5090, Los Angeles, California 90048,1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030,2 the Brain Research Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, 90095,3 Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, California, 900954

Received 1 February 2008/ Accepted 11 February 2008

Gene therapy is proposed as a novel therapeutic strategy for treating glioblastoma multiforme (GBM), a devastating brain cancer. In the clinic, antivector immune responses pose formidable challenges. Herein we demonstrate that high-capacity adenovirus vectors (HC-Ads) carrying the conditional cytotoxic gene herpes simplex virus type 1-thymidine kinase (TK) induce tumor regression and long-term survival in an intracranial glioma model, even in the presence of systemic antiadenovirus immunity, as could be encountered in patients. First-generation Ad-TK failed to elicit tumor regression in this model. These results pave the way for implementing HC-Ad-TK-mediated gene therapy as a powerful adjuvant for treating GBM.

* Corresponding author. Mailing address: Board of Governors’ Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Bldg., Research Pavilion, Rm. 5090, Los Angeles, CA 90048. Phone: (310) 423-7303. Fax: (310) 423-7308. E-mail: castromg{at}cshs.org

{triangledown} Published ahead of print on 20 February 2008.

Journal of Virology, May 2008, p. 4680-4684, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.00232-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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