437. Biosafety After the Injection of Carrier Cells Infected With Oncolytic Adenovirus

Abstract

Although replication-competent viruses have been developed to treat cancers, their cytotoxic effects are insufficient, since infection with them is inhibited by generation of neutralizing antibodies. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with oncolytic adenovirus were injected into syngeneic subcutaneous ovarian tumors after immunization with adenovirus and induced complete tumor regression by the induction of antiadenoviral and antitumoral CTL responses. To start clinical trial, toxicity and biodistribution study were carried out in nude mice, rabbits and beagle dogs. Acute toxicity and distribution test were carried out after the single injection of carrier cells into ovarian tumor in nude mice. Chronic toxicity test was carried out by 8 injections of carrier cells into rabbits for 4 weeks. Excretion study was carried out to determine whether oncolytic adenovirus was excreted from the beagle dogs after the single injection of carrier cells. Acute toxicity test did not show any lethal side effects in nude mice. In biodistribution test, single injection of carrier cells into ovarian tumor induced the peak levels of oncolytic adenovirus the next day but did not show any significant levels of that in nude mice 14 days after injection. In chronic toxicity test, 8 injections of 1.25×107 cells/kg or less did not show any significant toxicity in rabbits. In excretion test, oncolytic adenovirus was not excreted into the urine and the stool of beagle dogs. This oncolytic adenovirus-infected carrier cell system might prove effective and safe in the preclinical efficacy and the biosafety test, respectively. Clinical trial is being scheduled to treat recurrent solid cancers.