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

Wu J, Xiao X, Jia H, Chen J, Zhu Y, Zhao P, Lin H, Huang W - BMC Cancer (2009)

Bottom Line: 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).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).Disseminated Ad-IFNgamma DNA and the transgene product were mainly enriched in the liver.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, PR China. gladysw@163.com

ABSTRACT

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.

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Ad-IFNγ concentrations in the tumor, heart, liver, spleen, lung, kidney, brain, and blood at different time points after intratumoral injection of Ad-IFNγ. The dose of injection was 1 × 1010 VP/tumor. Data represent mean ± SD of three mice. Representative results from two independent experiments are shown.
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Figure 1: Ad-IFNγ concentrations in the tumor, heart, liver, spleen, lung, kidney, brain, and blood at different time points after intratumoral injection of Ad-IFNγ. The dose of injection was 1 × 1010 VP/tumor. Data represent mean ± SD of three mice. Representative results from two independent experiments are shown.

Mentions: Samples from tumor, heart, liver, spleen, lung, kidney, brain, and blood on days 1, 2, 3, 5, 7, 14 and 21, were tested for the amount of targeted DNA. The copy number of the targeted DNA in samples was deduced according to the standard curves. As shown in Fig. 1, Ad-IFNγ DNA was detected in tumor, blood, and parenchymal organs. Ad-IFNγ DNA was mainly enriched in tumors where the Ad-IFNγ DNA was injected (P < 0.05, compared to blood or parenchymal organs), then in livers (P < 0.05, compared to blood or other parenchymal organs). Concentrations of Ad-IFNγ DNA were very low in other organs and blood (Fig. 1). Ad-IFNγ DNA persisted for at least 7 days in the tumors. 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) (Table 1). Ad-IFNγ DNA in livers also decreased in a time-dependent manner and became undetectable at day 14 after intratumoral administration (Table 1).


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

Wu J, Xiao X, Jia H, Chen J, Zhu Y, Zhao P, Lin H, Huang W - BMC Cancer (2009)

Ad-IFNγ concentrations in the tumor, heart, liver, spleen, lung, kidney, brain, and blood at different time points after intratumoral injection of Ad-IFNγ. The dose of injection was 1 × 1010 VP/tumor. Data represent mean ± SD of three mice. Representative results from two independent experiments are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667533&req=5

Figure 1: Ad-IFNγ concentrations in the tumor, heart, liver, spleen, lung, kidney, brain, and blood at different time points after intratumoral injection of Ad-IFNγ. The dose of injection was 1 × 1010 VP/tumor. Data represent mean ± SD of three mice. Representative results from two independent experiments are shown.
Mentions: Samples from tumor, heart, liver, spleen, lung, kidney, brain, and blood on days 1, 2, 3, 5, 7, 14 and 21, were tested for the amount of targeted DNA. The copy number of the targeted DNA in samples was deduced according to the standard curves. As shown in Fig. 1, Ad-IFNγ DNA was detected in tumor, blood, and parenchymal organs. Ad-IFNγ DNA was mainly enriched in tumors where the Ad-IFNγ DNA was injected (P < 0.05, compared to blood or parenchymal organs), then in livers (P < 0.05, compared to blood or other parenchymal organs). Concentrations of Ad-IFNγ DNA were very low in other organs and blood (Fig. 1). Ad-IFNγ DNA persisted for at least 7 days in the tumors. 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) (Table 1). Ad-IFNγ DNA in livers also decreased in a time-dependent manner and became undetectable at day 14 after intratumoral administration (Table 1).

Bottom Line: 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).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).Disseminated Ad-IFNgamma DNA and the transgene product were mainly enriched in the liver.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, PR China. gladysw@163.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus