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.

CONCLUSION

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.