Dynamic distribution and expression in vivo of the human interferon gamma gene delivered by adenoviral vector.
BACKGROUND
We previously found that r-hu-IFNgamma exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts in vivo. Considering the fact that the clinical use of recombinant IFNgamma is limited by its short half-life and systemic side effects, we developed a recombinant adenovirus, Ad-IFNgamma.


METHODS
Dynamic distribution of the adenovirus vector and expression of IFNgamma were evaluated by Q-PCR and ELISA after intratumoral administration of Ad-IFNgamma into CNE-2 xenografts.


RESULTS
Ad-IFNgamma DNA was mainly enriched in tumors where the Ad-IFNgamma DNA was injected (P < 0.05, compared to blood or parenchymal organs), as well as in livers (P < 0.05). Concentrations of Ad-IFNgamma DNA in other organs and blood were very low. Intratumoral Ad-IFNgamma DNA decreased sharply at high concentrations (9 x 10(5) copies/microg tissue DNA), and slowly at lower concentrations (1.7-2.9 x 10(5) copies/microg tissue DNA). IFNgamma was detected in the tumors and parenchymal organs. The concentration of IFNgamma was highest in the tumor (P < 0.05), followed by the liver and kidney (P < 0.05). High-level intratumoral expression of IFNgamma was maintained for at least 7 days, rapidly peaking on day 3 after injection of Ad-IFNgamma DNA.


CONCLUSIONS
An IFNgamma gene delivered by an adenoviral vector achieved high and consistent intratumoral expression. Disseminated Ad-IFNgamma DNA and the transgene product were mainly enriched in the liver.
Wu
Jiangxue
J
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, PR China. gladysw@163.com
Xiao
Xia
X
Jia
Hongyun
H
Chen
Jiemin
J
Zhu
Yinghui
Y
Zhao
Peng
P
Lin
Huanxin
H
Huang
Wenlin
W
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D006801:Humans; D007267:Injections; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma