Neutralisation of adenovirus infectivity by ascitic fluid from ovarian cancer patients

Animal models and phase I clinical trials have shown that repeat virus deli very and subsequent transgene expression is limited by the generation of hu moral and cellular immune responses directed towards the therapeutic vector . The presence of a pre-existing immune response may even prevent initial d elivery. 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 f our matched serum samples were examined. The titre and isotype of anti-aden ovirus antibodies was determined by ELISA, and Western blotting identified the molecular basis of the immune response, which was primarily directed to wards fibre and penton base. Neutralisation of virus infectivity was assess ed in vitro by measurement of green fluorescent protein reporter gene expre ssion. We found that the ascitic fluid samples contain antibodies that reco gnise both adenovirus types 2 and 5, were predominantly IgG and directed to wards the viral antigens responsible for cell adhesion, and had virus neutr alising activity.