METHOD OF ADMINISTERING ADENOVIRUS

摘要

A method of reducing the risk associated with administering adenoviral particles to subjects undergoing adenoviral gene therapy. An extremely low titer of adenovirus neutralizing antibodies is believed to lead to an acute virus-mediated cytotoxicity. Neutralizing antibodies prevent the hepatotoxic effects of adenoviruses administered by way of the hepatic artery. An improved adenoviral gene therapy method of the type involving the administration, at a certain point in time, of recombinant adenoviruses containing a gene of interest to a subject wherein the improvement includes, before administering the recombinant adenovirus containing the gene of interest, providing the subject with neutralizing antibodies directed to the recombinant adenovirus. In one aspect of the method, the subject is provided with the antibodies by administering to the subject adenovirus of the same type as the recombinant adenovirus to be administered, at a before the administration of the recombinant adenovirus, to induce in the subject an immune response against the adenovirus. Alternatively, when insufficient time exists, or the subject is immunocompromised, the subject is directly provided with the neutralizing antibodies by administering, to the subject, antibodies directed against the same serotype of adenovirus as the recombinant adenovirus or antibodies cross-reactive with the serotype of the recombinant adenovirus. In such a case, the antibodies are administered about one hour before the administration of the recombinant adenovirus containing the gene of interest. In this aspect of the invention, human antibodies or humanized antibodies are particularly preferred to be administered parenterally to the subject.