Transduction of liver metastases after intravenous injection of Ad5/35 or Ad35 vectors with and without factor X-binding protein pretreatment

Ying Liu, Hongjie Wang, Roma Yumul, Wentao Gao, Andrea Gambotto, Takashi Morita, Andrew Baker, Dmitry Shayakhmetov, André Lieber

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)621-9
Number of pages9
JournalHuman Gene Therapy
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Adenoviridae
  • Animals
  • Antigens, CD46
  • CHO Cells
  • Carrier Proteins
  • Cell Line
  • Chemokines
  • Cricetinae
  • Cricetulus
  • Genetic Vectors
  • Humans
  • Injections
  • Injections, Intravenous
  • Liver Neoplasms
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oncolytic Virotherapy
  • Transduction, Genetic
  • Treatment Outcome
  • Virus Attachment

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