Transduction of liver metastases after intravenous injection of Ad5/35 or Ad35 vectors with and without factor X-binding protein pretreatment.
Inefficient tumor transduction with targeted adenoviral vectors is largely due to unspecific virus sequestration by blood components, including coagulation factor X, and Kupffer cell scavenging. In this study, we show that preinjection of snake venom factor X-binding protein (X-bp) reduces hepatocyte transduction and increases the circulation time in blood of an intravenously injected, fiber-chimeric Ad5/35 vector. X-bp pretreatment resulted in improved Ad5/35 transduction of liver metastases and increased the antitumor efficacy of an Ad5/35-based oncolytic adenovirus. Furthermore, we demonstrate that a vector based on adenoviral serotype 35, which is less sequestered by factor X, is efficient in tumor targeting. This gives a rationale for using Ad35-based vectors in virotherapy of cancer.
Liu
Ying
Y
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Wang
Hongjie
H
Yumul
Roma
R
Gao
Wentao
W
Gambotto
Andrea
A
Morita
Takashi
T
Baker
Andrew
A
Shayakhmetov
Dmitry
D
Lieber
André
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000494:pharmacology*; D002460:Cell Line; D018925:Chemokines / Q000097:blood; D006224:Cricetinae; D003412:Cricetulus; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007267:Injections; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary*; D051916:Membrane Cofactor Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050130:Oncolytic Virotherapy; D014161:Transduction, Genetic; D016896:Treatment Outcome; D053585:Virus Attachment / Q000187:drug effects
D002352:Carrier Proteins; D018925:Chemokines; D051916:Membrane Cofactor Protein; C431277:factor X-binding protein, Deinagkistrodon acutus