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Clinical immunology : the official journal of the Clinical Immunology Society v.183, 2017년, pp.240 - 246   SCI SCIE SCOPUS
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Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice

Ogura, Mineko (Department of Immunobiology, Yale University, New Haven, CT, United States ) ; Deng, Songyan (Department of Immunobiology, Yale University, New Haven, CT, United States ) ; Preston-Hurlburt, Paula (Department of Immunobiology, Yale University, New Haven, CT, United States ) ; Ogura, Hideki (Department of Immunobiology, Yale University, New Haven, CT, United States ) ; Shailubhai, Kunwar (Tiziana Life Sciences, R&D Center, 3805 Old Easton Road, Doylestown, PA 18902, United States ) ; Kuhn, Chantal (Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, United States ) ; Weiner, Howard L. (Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, United States ) ; Herold, Kevan C. (Department of Immunobiology, Yale University, New Haven, CT, United States ) ;
  • 초록  

    Abstract Oral administration of biologics may be a feasible approach for immune therapy that improves drug safety and potentiates mechanisms of tolerance at mucosal barriers. We tested the ability of a fully human non-FcR binding anti-CD3 mAb, foralumab, to prevent skin xenograft rejection in mice with human immune systems. At an intragastric dose of 15μg, the drug could transit through the small bowel. Serum absorption and binding of lymphoid cells was seen and proliferative responses of splenic CD8+ T cells to mitogen were reduced. Five consecutive daily doses, then weekly dosing led to indefinite graft acceptance without depletion of peripheral T cells. Proliferative and cytokine responses to activation of splenocytes with PHA were reduced. The serum levels of IL-10 but not TNF were increased 6days after application of the skin graft. Oral treatment with anti-CD3 mAb may represent a feasible approach for immune modulation. Highlights In humanized mice, intragastric anti-CD3 mAb prevents xenograft rejection. Anti-CD3 mAb passes through the stomach and small bowel and can be detected in the serum. Intragastric anti-CD3 mAb affects CD8+ T cell proliferation in the spleen and cytokine production. Anti-CD3 mAb treatment induces IL-10 release.


  • 주제어

    Anti-CD3 .   Monoclonal antibody .   Oral biologic .   Immune tolerance.  

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