The 4th Annual Tregitope update will be held in Baltimore Maryland on April 20th, 2012 (Click here for more information). Dr. Srini Kaveri of the Centre de Recherche des Cordeliers (INSERM) in Paris will provide an update on the mechanism of action of IVIG with an eye to parallels with Tregitope. A wide range of applications for Tregitopes, from autoimmunity to modulating the immune responses to protein therapeutics will be discussed by experts.
Tregitopes were discovered in 2008 by the team of De Groot and Martin at EpiVax; the original discovery was published in the journal Blood in 2008 [direct link to reference here]. These are linear sequences contained within the framework of monoclonal antibodies and immunoglobulin G (also known as gamma globulin). The Tregitopes act as a natural ‘off switch” and have been shown in standard preclinical models, and by collaborating laboratories, to suppress and treat autoimmune disease, allergy, and to effectively suppress the immunogenicity of co-administered proteins.
According to Dr. Kaveri, “It is most likely that some of the well established and successfully practiced therapeutic strategies such as intravenous immunoglobulins to treat several serious autoimmune and inflammatory diseases in order to induce tolerance, may actually be harnessing the potential of Tregitopes”.
Anticipated uses of Tregitope include induction of tolerance to co-administered protein drugs, a market worth more than $100B globally. Also known as biotherapeutics, drugs such as Campath, Rituximab, enzyme replacement therapies such as Myozyme, and blood factors such as FVIII often induce antibodies, rendering the drugs less effective or ineffective. The presence of Tregitopes in monoclonals is directly related to lower immunogenicity in clinical use, a finding that was previously described and published by De Groot and Martin.
In addition, Tregitopes may have broad applications in Transplant according Nader Najafian, M.D., who is using Tregitopes in research being performed at Harvard Brigham and Women’s Hospital, and therapy for autoimmune diseases such as Multiple Sclerosis. Researcher Samia Khoury M.D., an internationally recognized MS researcher also based at Harvard Brigham and Women’s hospital, says that pre-clinical studies of Tregitope being carried out in her laboratory by researcher Wassim Elyaman, Ph.D., are “promising”. The Tregitope technology won awards from the American Transplant Association (ATA) and from the American Association of Pharmacologists (AAPS) in 2010 and 2011.
For more information see the original publication: De Groot A.S., L. Moise, J.A. McMurry, Erik Wambre, Laurence Van Overvelt, Philippe Moingeon, W. Scott, W. Martin, Activation of Natural Regulatory T cells by IgG Fc-derived Peptide “Tregitopes”. Blood, 2008,112: 3303. http://tinyurl.com/ASDeGroot-Blood-2008. See also the publication by Elyaman and Khoury discussing the application of Tregitopes to MS by clicking here.