This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Google Scholar Google Scholar Articles by Hoffmann, D. Articles by Wildner, O. Search for Related Content PubMed PubMed Citation Articles by Hoffmann, D. Articles by Wildner, O.

Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Bochum, Germany

Requests for reprints: Oliver Wildner, Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Building MA, Room 6/40, D-44801 Bochum, Germany.Phone: 49-23432-27834; Fax: 49-23432-14352. E-mail: Oliver.Wildner{at}ruhr-uni-bochum.de

In our current study, we developed oncolytic adenoviruses which preferentially lyse pancreatic and colon cancer cells by replacing viral E1 and/or E4 promoter with the tumor/tissue-specific promoters, cyclooxygenase-2 (COX-2), midkine (MK), or the cell cycle–dependent promoter, E2F1. We generated three sets of recombinant adenoviral vectors. In the first set, only the native E1A promoter was replaced by the COX-2, MK, or E2F1 promoter, respectively. In the second set, the viral E4 promoter was substituted by these heterologous promoters and the viral E1A promoter was substituted by the ubiquitously active cytomegalovirus-IE promoter. In the third set, we substituted the viral E1A and E4 promoters with the COX-2, MK, or E2F1 promoter, respectively. In our system, transcriptional targeting of solitary viral E1A resulted in 50% enhanced restricted vector replication when compared with an unrestricted replication-competent adenovirus. Furthermore, a targeted expression of the viral E1A gene products had a greater effect on restricted adenoviral replication than that of the E4 region. With our vectors, Ad.COX·MK and Ad.MK·COX, using two different heterologous promoters to control E1A and E4 expression, we showed enhanced viral replication specificity when compared with Ad.COX·COX or Ad.MK·MK, respectively. In a s.c. xenograft tumor model, there was no significant difference in the antineoplastic efficacy of the double heterologous promoter–controlled vectors when compared with our unrestricted replication-competent control adenovirus or vectors with only E1A transcriptionally driven by a heterologous promoter. [Mol Cancer Ther 2006;5(2):374–81]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 9/16/05; revised 10/25/05; accepted 11/29/05.