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

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

  • Clin Immunol. 2017 Oct;183:240-246. doi: 10.1016/j.clim.2017.07.005.
Mineko Ogura 1,  Songyan Deng 1,  Paula Preston-Hurlburt 1,  Hideki Ogura 1,  Kunwar Shailubhai 2,  Chantal Kuhn 3,  Howard L Weiner 3,  Kevan C Herold 4
Affiliations

Affiliations

  • 1 Department of Immunobiology, Yale University, New Haven, CT, United States.
  • 2 Tiziana Life Sciences, R&D Center, 3805 Old Easton Road, Doylestown, PA 18902, United States.
  • 3 Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
  • 4 Department of Immunobiology, Yale University, New Haven, CT, United States; Department of Internal Medicine, Yale University, New Haven, CT, United States. Electronic address: kevan.herold@yale.edu.
PMID: 28739191 DOI: 10.1016/j.clim.2017.07.005
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.

Keywords

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

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