1. ¹Department of Microbiology, Immunology, and Pathology, Colorado State University, Ft Collins, CO, USA
2. ²Veterinary Cancer Specialists, Englewood, CO, USA
3. ³Department of Veterinary Medical Sciences, University of Wisconsin, Madison, WI, USA
4. ⁴Department of Comparative Medicine, University of Washington School of Medicine, Seattle, WA, USA
5. ⁵Department of Clinical Sciences, The Animal Cancer Center, Colorado State University, Ft Collins, CO, USA
6. ⁶The Valentis Corp, Burlingame, CA, USA
7. ⁷Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO, USA

Correspondence: Dr S Dow, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft Collins, CO 80523, USA. E-mail: sdow@colostate.edu

Received 4 April 2005; Revised 26 May 2005; Accepted 27 May 2005; Published online 2 September 2005.

Abstract

Intravenous gene delivery using liposome–DNA complexes (LDC) has previously been shown to elicit antitumor activity, but only in rodent tumor models. Therefore, we conducted a study to determine in a large animal spontaneous tumor model whether intravenous infusions of LDC could target gene expression to cutaneous tumor tissues and whether repeated treatments had an effect on tumor growth or angiogenesis. A total of 13 dogs with cutaneous soft tissue sarcomas were enrolled in the study and were randomized to receive a series of 6 weekly infusions of LDC containing either canine endostatin DNA or DNA encoding an irrelevant gene (luciferase). Serial tumor biopsies were obtained to assess transgene expression, tumor microvessel density (MVD), and intratumoral leukocyte inflammatory responses. We found that intravenous infusion of LDC did not result in detectable gene expression in cutaneous tumor tissues. However, two of 13 treated dogs had objective tumor responses and eight dogs had stable disease during the treatment period. In addition, a significant decrease in tumor MVD was noted in six of 12 treated dogs at the completion of six treatments. These results suggest that intravenous infusions of LDC may elicit nonspecific antitumor activity and inhibit tumor angiogenesis.