Endothelial cell-specific expression of tumor necrosis factor-alpha from the KDR or E-selectin promoters following retroviral delivery

Human Gene Therapy
R T JaggarR Bicknell

Abstract

The tumor vasculature offers a target for anti-cancer gene therapy which has the advantages both of good accessibility to systemically delivered therapy and comparative homogeneity across solid tumor types. We aimed to develop retroviruses carrying endothelial-specific promoters for the delivery of genes to proliferating endothelial cells in vitro and to tumor endothelial cells in vivo. This paper reports the generation of such retroviral vectors and the level of expression of murine tumor necrosis factor-alpha (mTNF-alpha) cDNA following infection into endothelial cells and stromal fibroblasts. Retroviral vectors carrying mTNF-alpha have been generated whose expression is controlled either by the retroviral long terminal repeat or by 5' proximal promoter sequences from the endothelial-specific kinase insert domain receptor (KDR)/VEGF receptor and E-Selectin promoters within the context of a self-inactivating (SIN) vector backbone. Both KDR and E-Selectin have been shown to be upregulated on tumor endothelium. A putative polyadenylation sequence AAATAAA within the E-Selectin promoter was mutated to permit faithful transmission of retroviral vectors carrying this promoter. We demonstrate a 10- to 11-fold increase in mTNF-alpha e...Continue Reading

References

Nov 11, 1991·Nucleic Acids Research·G LangD Kioussis
Apr 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M LewisD V Goeddel
Sep 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S N YaoK Kurachi
Mar 30, 1987·Biochemical and Biophysical Research Communications·L SchweigererD Gospodarowicz
Mar 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J P Dougherty, H M Temin
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·S F YuE Gilboa
Nov 1, 1982·British Journal of Cancer·J Denekamp, B Hobson
Sep 22, 1995·The Journal of Biological Chemistry·Q DangJ Taylor
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·F J Burrows, P E Thorpe
May 31, 1994·Annals of the New York Academy of Sciences·K SikoraN Lemoine
Jan 1, 1994·Annual Review of Medicine·K J Tracey, A Cerami
Dec 26, 1995·Biochemical and Biophysical Research Communications·B LiuL W Seymour

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Citations

Mar 24, 2005·Cancer Metastasis Reviews·Kevin J HarringtonHardev S Pandha
Mar 24, 2000·Trends in Genetics : TIG·D M NettelbeckR Müller
Nov 10, 2000·Advanced Drug Delivery Reviews·K J HarringtonR G Vile
Dec 4, 2001·Advanced Drug Delivery Reviews·Y S Haviv, D T Curiel
Sep 30, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hannah H ChenRobert C Carlisle
Jul 5, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Guillermo GarauletAntonio Rodríguez
Jul 24, 2001·The British Journal of Ophthalmology·I ChowersA Panet
Apr 2, 2004·The Journal of Clinical Investigation·Shoshana GreenbergerDror Harats
Jan 22, 2015·Viruses·Md Zahidul Islam Pranjol, Amin Hajitou
Apr 28, 2009·Advanced Drug Delivery Reviews·Zhihong Dong, Jacques E Nör
Jan 18, 2006·Reviews in Medical Virology·Adam M SonabendMaciej S Lesniak
May 4, 2004·Molecular and Cellular Neurosciences·Stefan IsenmannAlexandra Kretz
Jun 11, 2015·Journal of Drug Targeting·Jayoung KimJordan J Green
Sep 5, 2001·Gynecologic Oncology·E CasadoD T Curiel
Nov 7, 2006·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Keren LevanonDror Harats
Aug 17, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Luis G MeloVictor J Dzau
Jun 26, 2001·Gene Therapy·N Varda-BloomD Harats
Nov 11, 2006·Cancer Gene Therapy·M Bazan-PeregrinoA L Harris
Feb 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael PeledDror Harats
Mar 20, 2002·Clinical Oncology : a Journal of the Royal College of Radiologists·Kevin J HarringtonRichard G Vile

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