Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer.
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.
Affiliation: Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan; Department of Urology, St. Marianna University, Kanagawa, Japan.Show MeSH
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Mentions: To ascertain whether the combination of anti-GITR mAb enhances an antitumor immunity induced by the intratumoral IFN-α gene transfer, the antibody was intrapertitoneally administered at day 6 after the subcutaneous inoculation of Pan02 cells followed by intratumoral injection of Ad-mIFN at day 11. The injection of a lower dose (1 × 107 PFU) of Ad-mIFN showed the tumor suppressive effects not only in vector-injected right tumors but also in the vector-uninjected left tumors in anti-GITR mAb-treated mice compared with the injection of Ad-AP (Fig. 3a). Furthermore, the higher dose (5 × 107 PFU) of Ad-mIFN with anti-GITR mAb showed the stronger suppressive effect of Pan02 tumor growth at both sites compared with the lower dose adenovirus injection (Fig. 3b).
Affiliation: Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan; Department of Urology, St. Marianna University, Kanagawa, Japan.