Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery.

Published

Journal Article

Systemic virus dissemination is a potential problem during local gene delivery in solid tumours. However, the kinetics and pathways of the dissemination have not been well characterised during the first 24 h after the infusion is started. To this end, we infused adenoviral vectors for luciferase or enhanced green fluorescence protein into three different tumour models in mice. During and/or after the infusion, we determined the amount of adenoviruses in the tumour, blood, and liver, and examined the transgene expression in the liver, lung, blood, and tumour. In addition, we intravenously injected tumour cells expressing luciferase and examined the biodistribution of these cells in the body. We observed transgene expression in the liver and tumour at 24 h after the infusion, but could not detect transgene expression in the blood and lung. The peak concentration of viral vectors in the plasma occurred during the intratumoral infusion. At 10 min after the infusion, few viral vectors remained in the blood and the ratio of copy numbers of adenoviruses between liver and tumour was > 2 in 80% and > or = 10 in 40% of the mice. Most tumour cells injected intravenously accumulated in the lung within the first 24 h. Taken together, these data indicated that systemic virus dissemination occurred mainly during the first 10 min after the intratumoral infusion was started, and that the dissemination was due to infusion-induced convective transport of viral vectors into leaky tumour microvessels.

Full Text

Duke Authors

Cited Authors

  • Wang, Y; Yang, Z; Liu, S; Kon, T; Krol, A; Li, C-Y; Yuan, F

Published Date

  • April 25, 2005

Published In

Volume / Issue

  • 92 / 8

Start / End Page

  • 1414 - 1420

PubMed ID

  • 15812558

Pubmed Central ID

  • 15812558

International Standard Serial Number (ISSN)

  • 0007-0920

Digital Object Identifier (DOI)

  • 10.1038/sj.bjc.6602494

Language

  • eng

Conference Location

  • England