The discovery of natural regulatory T cell epitopes (Tregitopes) in the sequence of therapeutics mAbs represents a paradigm shift for protein therapeutics, allergy, autoimmunity and transplantation. Tregitopes are currently being evaluated in vitro and in vivo in five collaborating academic laboratories. For example, investigations in Transplantation (MLR, cardiac transplant model) are being carried out by Mo Sayegh and Nader Najafian (Transplantation Research Center, Brigham and Woman's Hospital and Children's Hospital Boston, Harvard Medical School), in protein therapeutics (FVIII) and autoimmunity (Type 1 Diabetes) by David Scott (Department of Surgery, Microbiology, University of Maryland School of Medicine), in Multiple Sclerosis by Samia Khoury (Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School), have demonstrated the Tregitopes activate natural Tregs and induce adoptive tolerance to a range of target antigens. Current studies are focusing on dose, delivery and route of administration to maximize the Tregitope effect. Safety is expected to be excellent, as Tregitopes are believed to be the active component of a widely used immunotherapy, IVIG.
Tregitopes are a set of peptides that specifically activate CD4+CD25+FoxP3+ natural regulatory T cells (nTregs). Tregitopes are promiscuous MHC Class II T cell epitopes located in the Fc and framework regions of Fab from IgG. In vitro, co-incubation of antigens with Tregitopes in vitro leads to a suppression of effector cytokine and chemokine secretion, reduced proliferation of effector T cells, and expansion of antigen-specific adaptive Tregs (aTregs). In vivo,
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