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Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer.

Aida K, Miyakawa R, Suzuki K, Narumi K, Udagawa T, Yamamoto Y, Chikaraishi T, Yoshida T, Aoki K - Cancer Sci. (2014)

Bottom Line: First we showed that an intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model.The CCR5 expression on Tregs was downregulated in the antibody-treated mice, which may explain the decrease of tumor-infiltrating Tregs.The combination of Treg-suppression by GITR mAb and the tumor immunity induction by IFN-α gene therapy could be a promising therapeutic strategy for pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan; Department of Urology, St. Marianna University, Kanagawa, Japan.

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Adenovirus-mediated intratumoral inter-feron (IFN)-α gene transfer induces a systemic antitumor effect. Pan02 cells were inoculated on both legs in C57BL/6 mice, and 11 days later various amounts (1 × 107, 5 × 107, 5 × 108 PFU) of Ad-mIFN or Ad-AP were injected into the subcutaneous tumor on the right leg (n = 4). Data are representative of two separate experiments with similar results.
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fig01: Adenovirus-mediated intratumoral inter-feron (IFN)-α gene transfer induces a systemic antitumor effect. Pan02 cells were inoculated on both legs in C57BL/6 mice, and 11 days later various amounts (1 × 107, 5 × 107, 5 × 108 PFU) of Ad-mIFN or Ad-AP were injected into the subcutaneous tumor on the right leg (n = 4). Data are representative of two separate experiments with similar results.

Mentions: To examine the in vivo antitumor effect of the IFN-α gene transduction, various amounts (1 × 107, 5 × 107 and 5 × 108 PFU) of Ad-mIFN were injected into the right tumors in the mice with Pan02 tumors on both legs. The injection showed remarkable tumor suppressive effects not only in the vector-injected right tumors but also in the vector-uninjected left tumors in a dose-dependent manner (Fig. 1). The tumor suppressive effect was stronger in the right tumors than in the left tumors, possibly due to the direct anti-proliferative effect of IFN-α in Pan02 cells (data not shown) in addition to an induction of antitumor immunity. Tumor volumes were not changed in the mice treated by intratumoral injection of Ad-AP at 5 × 108 PFU as compared with the no treatment group (Fig. 1).


Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer.

Aida K, Miyakawa R, Suzuki K, Narumi K, Udagawa T, Yamamoto Y, Chikaraishi T, Yoshida T, Aoki K - Cancer Sci. (2014)

Adenovirus-mediated intratumoral inter-feron (IFN)-α gene transfer induces a systemic antitumor effect. Pan02 cells were inoculated on both legs in C57BL/6 mice, and 11 days later various amounts (1 × 107, 5 × 107, 5 × 108 PFU) of Ad-mIFN or Ad-AP were injected into the subcutaneous tumor on the right leg (n = 4). Data are representative of two separate experiments with similar results.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317823&req=5

fig01: Adenovirus-mediated intratumoral inter-feron (IFN)-α gene transfer induces a systemic antitumor effect. Pan02 cells were inoculated on both legs in C57BL/6 mice, and 11 days later various amounts (1 × 107, 5 × 107, 5 × 108 PFU) of Ad-mIFN or Ad-AP were injected into the subcutaneous tumor on the right leg (n = 4). Data are representative of two separate experiments with similar results.
Mentions: To examine the in vivo antitumor effect of the IFN-α gene transduction, various amounts (1 × 107, 5 × 107 and 5 × 108 PFU) of Ad-mIFN were injected into the right tumors in the mice with Pan02 tumors on both legs. The injection showed remarkable tumor suppressive effects not only in the vector-injected right tumors but also in the vector-uninjected left tumors in a dose-dependent manner (Fig. 1). The tumor suppressive effect was stronger in the right tumors than in the left tumors, possibly due to the direct anti-proliferative effect of IFN-α in Pan02 cells (data not shown) in addition to an induction of antitumor immunity. Tumor volumes were not changed in the mice treated by intratumoral injection of Ad-AP at 5 × 108 PFU as compared with the no treatment group (Fig. 1).

Bottom Line: First we showed that an intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model.The CCR5 expression on Tregs was downregulated in the antibody-treated mice, which may explain the decrease of tumor-infiltrating Tregs.The combination of Treg-suppression by GITR mAb and the tumor immunity induction by IFN-α gene therapy could be a promising therapeutic strategy for pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan; Department of Urology, St. Marianna University, Kanagawa, Japan.

Show MeSH
Related in: MedlinePlus