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

Liu, Y., Wang, H.J., Yumul, R., Gao, W.T., Gambotto, A., Morita, T., Baker, A.H., Shayakhmetov, D. and Lieber, A. (2009) Transduction of liver metastases after intravenous injection of Ad5/35 or Ad35 vectors with and without factor X-binding protein pretreatment. Human Gene Therapy, 20(6), pp. 621-629. (doi: 10.1089/hum.2008.142)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Baker, Professor Andrew
• Authors: Liu, Y., Wang, H.J., Yumul, R., Gao, W.T., Gambotto, A., Morita, T., Baker, A.H., Shayakhmetov, D., and Lieber, A.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: Human Gene Therapy
• ISSN: 1043-0342
• ISSN (Online): 1557-7422
• Published Online: 06 April 2009