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Journal of Virology, April 2006, p. 3904-3911, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3904-3911.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Characterization of the Recombinant Adenovirus Vector AdYB-1: Implications for Oncolytic Vector Development

Gabriel Glockzin,^1,2 Klaus Mantwill,¹ Karsten Jurchott,³ Alexandra Bernshausen,¹ Axel Ladhoff,³ Hans-Dieter Royer,⁴ Bernd Gansbacher,¹ and Per Sonne Holm^1,5*

Institut fuer Experimentelle Onkologie und Therapieforschung, Technische Universitaet Muenchen, Klinikum rechts der Isar, Munich, Germany,¹ Department of Surgery, University of Regensburg Medical Centre, Regensburg, Germany,² Max-Delbrueck Centrum für Molekulare Medizin, Berlin, Germany,³ Center of Advanced European Studies and Research (CAESAR), Bonn, Germany,⁴ XVir Therapeutics GmbH, Munich, Germany⁵

Received 27 July 2005/ Accepted 18 January 2006

Conditionally replicating adenoviruses are a promising new modality for the treatment of cancer. However, early clinical trials demonstrate that the efficacy of current vectors is limited. Interestingly, DNA replication and production of viral particles do not always correlate with virus-mediated cell lysis and virus release depending on the vector utilized for infection. However, we have previously reported that nuclear accumulation of the human transcription factor YB-1 by regulating the adenoviral E2 late promoter facilitates viral DNA replication of E1-deleted adenovirus vectors which are widely used for cancer gene therapy. Here we report the promotion of virus-mediated cell killing as a new function of the human transcription factor YB-1. In contrast to the E1A-deleted vector dl312 the first-generation adenovirus vector AdYB-1, which overexpresses YB-1 under cytomegalovirus promoter control, led to necrosis-like cell death, virus production, and viral release after infection of A549 and U2OS tumor cell lines. Our data suggest that the integration of YB-1 in oncolytic adenoviruses is a promising strategy for developing oncolytic vectors with enhanced potency against different malignancies.

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* Corresponding author. Mailing address: Institut fuer Experimentelle Onkologie und Therapieforschung, Technische Universitaet Muenchen, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany. Phone: 49-89-4140-4462. Fax: 49-89-4140-4476. E-mail: per.s.holm{at}lrz.tum.de.

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Journal of Virology, April 2006, p. 3904-3911, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3904-3911.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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