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Tumor Biology 8: Tumor Angiogenesis and the Microenvironment 1

Genetic targeting of endothelial populations for therapeutic applications

Timothy F. Lane and Luisa Iruela-Arispe
Timothy F. Lane
UCLA, Johnsson Comprehensive Cancer Ctr., Los Angeles, CA and University of California, Los Angeles, Los Angeles, CA
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Luisa Iruela-Arispe
UCLA, Johnsson Comprehensive Cancer Ctr., Los Angeles, CA and University of California, Los Angeles, Los Angeles, CA
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DOI:  Published April 2006
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Proc Amer Assoc Cancer Res, Volume 47, 2006

Abstract

1046

We have identified a transgenic enhancer cassette derived from cadherin 5 (VE-cadherin, VECAD) gene that directs gene expression in a subset of bone marrow cells that include endothelial cell progenitors (BMD-ECP). In the present report we describe the creation and initial characterization of a family of lentiviral expression cassettes using the VECAD genetic element. Preliminary studies with VEcad-GFP lentiviral vectors indicated utility in marking a variety of endothelial cell types, including those from large and small blood vessels and from arterial and venous vessels. Expression in non-endothelial cells was not detected. A second family of cad5 promoter vectors was created to carry hsv thymidine kinase (hsvTK). hsvTK is widely used in gene therapy vectors because of its specific ability to convert the prodrug gancyclovir into a cytotoxic thymidine analog p-gancyclovir. VEcad-hsvTK infected endothelial cells displayed high levels of killing in response to treatment with gancyclovir. Killing was both dose and time dependent and was restricted to endothelial targets. In vitro experiments with a variety of endothelial and non endothelial cell lines indicated that killing by gancyclovir was EC specific and required both the presence VEcad-hsvTK lentivirus and gancylovir. Experiments are currently underway to test the efficacy and specificity of this approach for in vivo labeling and tracking of BMD-ECP in mice.

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Cancer Research: 66 (8 Supplement)
April 2006
Volume 66, Issue 8 Supplement
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Genetic targeting of endothelial populations for therapeutic applications
Timothy F. Lane and Luisa Iruela-Arispe
Cancer Res April 15 2006 (66) (8 Supplement) 247;

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Genetic targeting of endothelial populations for therapeutic applications
Timothy F. Lane and Luisa Iruela-Arispe
Cancer Res April 15 2006 (66) (8 Supplement) 247;
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Show more Tumor Biology 8: Tumor Angiogenesis and the Microenvironment 1
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