Antiangiogenic gene therapy of cancer utilizing a recombinant adenovirus to elevate systemic endostatin levels in mice.
Gene therapy represents a possible alternative to the chronic delivery of recombinant antiangiogenic proteins to cancer patients. Inducing normal host tissues to produce high circulating levels of these proteins may be more effective than targeting antiangiogenic genes to tumor tissue specifically. Previously reported gene therapy approaches in mice have achieved peak circulating endostatin levels of 8-33 ng/ml. Here we report plasma endostatin levels of 1770 ng/ml after administration of a recombinant adenovirus. Growth of MC38 adenocarcinoma, which is relatively resistant to adenoviral infection, was inhibited by 40%. These findings encourage gene delivery approaches that use the host as a "factory" to produce high circulating levels of antiangiogenic agents.
Feldman
A L
AL
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Restifo
N P
NP
Alexander
H R
HR
Bartlett
D L
DL
Hwu
P
P
Seth
P
P
Libutti
S K
SK
D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D003094:Collagen / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D043169:Endostatins; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D003094:Collagen