Intravenous readministration of an adenoviral vector performed long after the initial administration failed to induce re-expression of the original transgene in rats.
Although most humans have been exposed to wild-type adenoviruses in their childhood, titers of neutralizing antibodies against viruses decrease with the passage of time. In the present study, we infused adenoviruses carrying the lacZ gene into the tail vein of rats, and re-infused the same adenoviruses long after the initial administration. However, development of neutralizing antibodies against adenovirus and proliferation of adenovirus-specific T cells were elicited profoundly by adenoviral readministration, and transgene expression was not induced in rats. Our results may have important implications for efficacy considerations when adenoviral vectors are employed in clinical settings for the treatment of cancer.
Tsujinoue
H
H
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Kuriyama
S
S
Tominaga
K
K
Okuda
H
H
Nakatani
T
T
Yoshiji
H
H
Tsujimoto
T
T
Akahane
T
T
Asada
K
K
Fukui
H
H
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007763:Lac Operon / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology