INHIBITORY EFFECTS OF HUMAN SERA ON ADENOVIRUS-MEDIATED GENE-TRANSFERINTO RAT-LIVER

Recent advances in molecular biology have made gene therapy for cancer feasible in clinical trials Although recombinant adenovirus is an att ractive vehicle for transferring therapeutic genes in vivo, animal stu dies have indicated that the clinical usefulness of adenovirus vectors may be limited by their immunogenicity. It has been shown that neutra lizing antibodies against adenoviruses reduce the efficiency of vector readministration. It is of great importance to examine the effects of human sera on adenovirus-mediated gene transfer, because the majority of prospective gene therapy patients are likely to have been exposed to wild-type adenoviruses. In the present study it was shown that anti -adenovirus antibody-positive human sera with the lowest positive tite r substantially inhibit the adenovirus-mediated gene transfer not only in vitro but also in vivo. These results may have important implicati ons for efficacy considerations when adenovirus vectors are employed i n the clinical setting.