Kevan Herold

Yale University School of Medicine, USA

Title: Immune therapies for autoimmune diseases: Thinking out of the box

Abstract:

New immune therapies are in clinical testing that appear able to modulate the natural history of a number of autoimmune diseases. These therapies are more selective in their targets which can improve their safety but can also result in new toxicities when these targets are expressed on many tissues. The results of clinical studies of immune therapies in autoimmune diseases such as Type 1 diabetes and multiple sclerosis have necessitated a reconsideration of results from preclinical models of human disease. In particular the kinetics of the disease process in animal models and human disease need to be carefully considered in view of data that has shown, for example, that targeting B cells at the time of disease onset can even affect diseases that have traditionally been thought to be primarily T cell mediated such as multiple sclerosis and Type 1 diabetes. These findings highlight the complexity of the mechanisms of autoimmune responses that lead to disease as well as the effects of new immune therapies. Antibodies against T cell specific markers such as CD3 may modulate disease not by depletion of T effector cells but rather by modulating the number and/or function of regulatory cell populations. Despite the promising results from preclinical models, permanent remissions of disease have generally not been achieved. This may reflect the intersection of the disease specific biology with immune mechanisms. Combination therapies with agents that can arrest autoimmunity with those that directly affect tissues may be required to successfully eradicate autoimmune diseases.

Biography:

Dr. Kevan Herold is Professor of Immunobiology and Medicine at Yale University. The focus of his investigative work is on developing new ways to prevent and treat Type 1 diabetes. He has studied and is developing novel immunologic and metabolic approaches that have been able to prevent the progression of Type 1 diabetes and is involved in a number of national and international clinical studies of new treatments. He is the Director of the TrialNet Center at Yale. He and his colleagues initially reported on the use of an anti-CD3 monoclonal antibody to treat patients with new onset Type 1 diabetes, that is now in development for treatment. His laboratory studies which involve both patient samples and models of Type 1 diabetes focus on the mechanisms of immune regulation, with the goal of improving on this initial success with anti-CD3 antibody and achieving a stable reversal of diabetes. These studies also involve the use and stimulation of islet stem cells to regenerate insulin producing cells that are lost during development of diabetes. His clinical interests are in management of diabetes, complications of diabetes, and complications as well as other Endocrine diseases.