Abstract 590: Preclinical biosafety test of oncolytic adenovirus-infected carrier cell for Phase I study

Abstract

Abstract Although almost 1000 clinical trials of gene therapy have been tried in USA, any significant clinical effects have not yet been reported. This is due to the anti-viral neutralizing antibodies production after the induction of viral mediated gene delivery for clinical trials. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with oncolytic adenovirus were incubated with target ovarian cancer cells in high titer of antiadenovirus antibody. Carrier cells were injected into syngeneic subcutaneous ovarian tumors after immunization with adenovirus. Carrier cell-derived cell fragments containing viral particles were engulfed by proliferative target ovarian cancer cells. This engulfment-mediated transfer of adenovirus was not inhibited by antiadenovirus antibody and enabled repetitive infection. After the induction of antiadenoviral CTL responses by immunization of adenovirus, administration of carrier cells infected with a replication-competent adenovirus induced complete tumor regression. Short term toxicity and distribution test were carried out to inject carrier cells into ovarian tumor in nude mice at once and long term toxicity test was carried out to inject carrier cells into rabbits at 8 times for 4 weeks. Short term toxicity test did not show any lethal side effects in nude mice. In distribution test, single injection of carrier cells into ovarian tumor induced the peak levels of cells and oncolytic virus in tumors on the next day but did not show any significant levels of cells and oncolytic virus in tumors 14 days after injection. In long term toxicity test, 8 injections of carrier cells (1.25 × 107 cells/kg) did not show any significant toxicity in rabbits This novel adenoviral receptor independent carrier cell-mediated viral transfection system might prove safe in this preclinical biosafety test and useful to treat solid tumors. Phase I clinical trial of this carrier cells infected with oncolytic adenovirus will be started soon to treat recurrent solid tumors which is resistant to the common treatment of surgery, radiation and chemotherapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 590.