Increased therapeutic efficacy of the prostate-specific oncolytic adenovirus Ad[I/PPT-E1A] by reduction of the insulator size and introduction of the full-length E3 region

Cancer Gene Therapy
A DanielssonMagnus Essand

Abstract

Conditionally replicating adenoviruses are developing as a complement to traditional cancer therapies. Ad[I/PPT-E1A] is an E1B/E3-deleted virus that replicates exclusively in prostate cells, since the expression of E1A is controlled by the recombinant 1.4 kb prostate-specific PPT promoter. The transcriptional integrity of PPT is maintained by the 3.0 kb mouse H19 insulator that was introduced directly upstream of the PPT sequence. In order to increase the cloning capacity to be able to reintroduce E3 sequences in the 35.7 kb Ad[I/PPT-E1A] genome, various shorter insulators were examined in a luciferase reporter gene assay. It was found that the 1.6 kb core H19 insulator (i) improves the activity of PPT, compared to the 3.0 kb full-length insulator, while still maintaining prostate cell specificity and releasing 1.4 kb of space for insertion of additional sequences. To improve the ability of the virus to efficiently lyse infected cells and persist in vivo, we inserted the adenovirus death protein (ADP) or the full-length adenovirus E3 region. The oncolytic activity of PPT-E1A-based viruses was studied using MTS, crystal violet and replication assays. The virus with the reintroduced full-length E3-region (Ad[i/PPT-E1A, E3]) showe...Continue Reading

References

Oct 1, 1993·Journal of Virology·A J BettF L Graham
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Jun 30, 2000·Current Biology : CB·A P Wolffe
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·M EdingerC H Contag
Oct 20, 2000·The Journal of General Virology·W C Russell
Mar 3, 2001·Neoplasia : an International Journal for Oncology Research·A RehemtullaB D Ross
Jan 5, 2002·The Journal of Biological Chemistry·Vasudeva GinjalaRolf Ohlsson
Mar 19, 2003·Lancet·Henrik Grönberg
Jul 25, 2003·The New England Journal of Medicine·William G NelsonWilliam B Isaacs
Dec 24, 2003·International Reviews of Immunology·Drew L LichtensteinWilliam S M Wold
Feb 24, 2004·The Journal of Gene Medicine·Marshall S Horwitz
May 4, 2004·International Journal of Cancer. Journal International Du Cancer·Anna Kanerva, Akseli Hemminki
Aug 6, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wing-Shing ChengMagnus Essand
Nov 18, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kenneth N BartonSvend O Freytag

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Citations

Jul 3, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mohanraj RamachandranFredrik Eriksson
Dec 2, 2009·Human Gene Therapy·Jeroen de VrijGuy Zuber
Sep 16, 2009·Briefings in Functional Genomics & Proteomics·Eduardo MoltóLluís Montoliu
Aug 4, 2011·Journal of Invertebrate Pathology·Guillermo C Rivera-GonzalezNorman J Maitland
May 16, 2012·Cell Transplantation·Christian MolnárOlle Korsgren
Jan 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emma ErikssonAngelica Loskog
Jul 23, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohanraj RamachandranMagnus Essand
May 2, 2020·Cancer Gene Therapy·Jessica WentheAngelica Loskog
Apr 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eduardo G CafferataOsvaldo L Podhajcer
May 26, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Emma ErikssonAngelica Loskog
Jan 15, 2011·Cancer Research·Munitta MuthanaNorman J Maitland

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