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Παρασκευή 21 Ιουλίου 2017

Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice

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Publication date: Available online 21 July 2017
Source:Clinical Immunology
Author(s): Mineko Ogura, Songyan Deng, Paula Preston-Hurlburt, Hideki Ogura, Kunwar Shailubhai, Chantal Kuhn, Howard L. Weiner, Kevan C. Herold
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.



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