Liposome-DNA complexes infused intravenously inhibit tumor angiogenesis and elicit antitumor activity in dogs with soft tissue sarcoma.
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.
Kamstock
D
D
Department of Microbiology, Immunology, and Pathology, Colorado State University, Ft Collins, 80523, USA.
Guth
A
A
Elmslie
R
R
Kurzman
I
I
Liggitt
D
D
Coro
L
L
Fairman
J
J
Dow
S
S
D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D004283:Dog Diseases / Q000378:metabolism / Q000517:prevention & control*; D004285:Dogs; D043169:Endostatins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005354:Fibrosarcoma / Q000098:blood supply / Q000628:therapy / Q000662:veterinary; D005822:Genetic Vectors; D007262:Infusions, Intravenous; D008081:Liposomes / Q000008:administration & dosage; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000662:veterinary*; D012509:Sarcoma / Q000098:blood supply / Q000378:metabolism / Q000662:veterinary*; D012878:Skin Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000662:veterinary*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D019076:Transgenes / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043169:Endostatins; D008081:Liposomes; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D004247:DNA; D008156:Luciferases