Inhibitory effects of human sera on adenovirus-mediated gene transfer into rat liver.
Recent advances in molecular biology have made gene therapy for cancer feasible in clinical trials. Although recombinant adenovirus is an attractive vehicle for transferring therapeutic genes in vivo, animal studies have indicated that the clinical usefulness of adenovirus vectors may be limited by their immunogenicity. It has been shown that neutralizing 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 titer substantially inhibit the adenovirus-mediated gene transfer not only in vitro but also in vivo. These results may have important implications for efficacy considerations when adenovirus vectors are employed in the clinical setting.
Third Department of Internal Medicine, Nara Medical University, Japan.
S
S
Kuriyama
K
K
Tominaga
M
M
Kikukawa
T
T
Nakatani
H
H
Tsujinoue
M
M
Yamazaki
S
S
Nagao
Y
Y
Toyokawa
A
A
Mitoro
H
H
Fukui
D016475:3T3 Cells; D000256:Adenoviridae; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001769:Blood; D002460:Cell Line; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007668:Kidney; D008099:Liver / Q000166:cytology / Q000502:physiology*; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000096:biosynthesis
D000914:Antibodies, Viral; D011994:Recombinant Proteins; D001616:beta-Galactosidase