Dynamic distribution and expression <it>in vivo </it>of the human interferon gamma gene delivered by adenoviral vector

• Main Authors: Zhao Peng, Zhu Yinghui, Chen Jiemin, Jia Hongyun, Xiao Xia, Wu Jiangxue, Lin Huanxin, Huang Wenlin
• Format: Article
• Language: English
• Published: BMC 2009-02-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/9/55

<p>Abstract</p> <p>Background</p> <p>We previously found that r-hu-IFNγ exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts <it>in vivo</it>. Considering the fact that the clinical use of recombinant IFNγ is limited by its short half-life and systemic side effects, we developed a recombinant adenovirus, Ad-IFNγ.</p> <p>Methods</p> <p>Dynamic distribution of the adenovirus vector and expression of IFNγ were evaluated by Q-PCR and ELISA after intratumoral administration of Ad-IFNγ into CNE-2 xenografts.</p> <p>Results</p> <p>Ad-IFNγ DNA was mainly enriched in tumors where the Ad-IFNγ DNA was injected (<it>P </it>< 0.05, compared to blood or parenchymal organs), as well as in livers (<it>P </it>< 0.05). Concentrations of Ad-IFNγ DNA in other organs and blood were very low. Intratumoral Ad-IFNγ DNA decreased sharply at high concentrations (9 × 10⁵copies/μg tissue DNA), and slowly at lower concentrations (1.7–2.9 × 10⁵copies/μg tissue DNA). IFNγ was detected in the tumors and parenchymal organs. The concentration of IFNγ was highest in the tumor (<it>P </it>< 0.05), followed by the liver and kidney (<it>P </it>< 0.05). High-level intratumoral expression of IFNγ was maintained for at least 7 days, rapidly peaking on day 3 after injection of Ad-IFNγ DNA.</p> <p>Conclusion</p> <p>An IFNγ gene delivered by an adenoviral vector achieved high and consistent intratumoral expression. Disseminated Ad-IFNγ DNA and the transgene product were mainly enriched in the liver.</p>