Open Access Research article

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

Jiangxue Wu1, Xia Xiao1, Hongyun Jia13, Jiemin Chen1, Yinghui Zhu1, Peng Zhao1, Huanxin Lin1 and Wenlin Huang12*

Author Affiliations

1 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China

2 Institute of Microbiology, Chinese Academy of Science, Beijing 100080, PR China

3 College of fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China

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BMC Cancer 2009, 9:55  doi:10.1186/1471-2407-9-55

Published: 16 February 2009

Abstract

Background

We previously found that r-hu-IFNγ exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts in vivo. 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.

Methods

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.

Results

Ad-IFNγ DNA was mainly enriched in tumors where the Ad-IFNγ DNA was injected (P < 0.05, compared to blood or parenchymal organs), as well as in livers (P < 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 × 105 copies/μg tissue DNA), and slowly at lower concentrations (1.7–2.9 × 105 copies/μg tissue DNA). IFNγ was detected in the tumors and parenchymal organs. The concentration of IFNγ was highest in the tumor (P < 0.05), followed by the liver and kidney (P < 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.

Conclusion

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.