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  • Viral Transfer Technology
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Neutralisation of adenovirus infectivity by ascitic fluid from ovarian cancer patients

Gene Therapy volume 7, pages 637–643 (2000)Cite this article

Abstract

Animal models and phase I clinical trials have shown that repeat virus delivery and subsequent transgene expression is limited by the generation of humoral and cellular immune responses directed towards the therapeutic vector. The presence of a pre-existing immune response may even prevent initial delivery. In order to determine the presence of pre-existing anti-adenovirus humoral immunity we analysed ascitic fluid, collected from the peritoneal cavity of patients with advanced ovarian cancer. Twelve ascitic fluid and four matched serum samples were examined. The titre and isotype of anti-adenovirus antibodies was determined by ELISA, and Western blotting identified the molecular basis of the immune response, which was primarily directed towards fibre and penton base. Neutralisation of virus infectivity was assessed in vitro by measurement of green fluorescent protein reporter gene expression. We found that the ascitic fluid samples contain antibodies that recognise both adenovirus types 2 and 5, were predominantly IgG and directed towards the viral antigens responsible for cell adhesion, and had virus neutralising activity.

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Acknowledgements

We would like to thank Drs Moira Gilligan and Rachael Barton for the collection of ascitic fluid and serum samples and Dr Peter Searle for construction of Ad-CMV-gfpΔE1. We are indebted to Dr Leonard Seymour for stimulating discussions and critical reading of the manuscript. This work was supported by the Cancer Research Campaign and the Medical Research Council.

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  1. CRC Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TA, UK

    Y Stallwood, K D Fisher, P H Gallimore & V Mautner

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  1. Y Stallwood
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  2. K D Fisher
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  3. P H Gallimore
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  4. V Mautner
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Stallwood, Y., Fisher, K., Gallimore, P. et al. Neutralisation of adenovirus infectivity by ascitic fluid from ovarian cancer patients. Gene Ther 7, 637–643 (2000). https://doi.org/10.1038/sj.gt.3301152

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