title: Transduction of liver metastases after intravenous injection of Ad5/35 or Ad35 vectors with and without factor X-binding protein pretreatment.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Roma
authors.initials: R
authors.lastname: Yumul
authors.forename: Wentao
authors.initials: W
authors.lastname: Gao
authors.forename: Andrea
authors.initials: A
authors.lastname: Gambotto
authors.forename: Takashi
authors.initials: T
authors.lastname: Morita
authors.forename: Andrew
authors.initials: A
authors.lastname: Baker
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shayakhmetov
authors.forename: André
authors.initials: A
authors.lastname: Lieber
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D018925:Chemokines; D051916:Membrane Cofactor Protein; C431277:factor X-binding protein, Deinagkistrodon acutus