Dynamic distribution and expression in vivo of the human interferon gamma gene delivered by adenoviral vector
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
BMC Cancer 2009, 9:55 doi:10.1186/1471-2407-9-55Published: 16 February 2009
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.
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.
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.
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.