FORIMMUN

RESEARCH NETWORK FOR NEW STRATEGIES IN IMMUNOTHERAPY

M2 M2 - Therapy of autoimmune diseases by expansion and activation of regulatory T cells

Research issues:
Autoimmunity - the pathological immune response to self tissues and cells - is thought to originate from an imbalance between disease inducing autoreactive T-cells and their counterparts, the so-called regulatory T-cells. Thus, the reduced frequency of regulatory T-cells observed in patients with type I diabetes is supposed to contribute to the pathogenesis of this autoimmune disease. Therefore, novel immune therapies capable of increasing numbers or enhancing effector functions of regulatory T-cells should provide a means for the effective and targeted treatment of autoimmune diseases.

Results:
In the course of a collaboration between the Institute for Virology and Immunobiology of the University of Würzburg and the company Tegenero AG, we generated so-called superagonistic CD28-specific monoclonal antibodies having the potency to expand regulatory T cells both in vitro and in vivo. In addition to this quantitative effect, these antibodies are also able to enhance the suppressive activity of regulatory T cells allowing for a more efficient control of autoreactive T-cells. We investigated the therapeutic potential of CD28-stimulated regulatory T cells in experimental autoimmune neuritis (EAN), an animal model of a human autoimmune disease affecting the peripheral nervous system (Guillain-Barre-Syndrome). First experimental results showed that superagonisitc CD28-specific antibody-treatment causes a delay in onset and an amelioration of the severity of EAN. Taken together, our results indicate that this novel class of CD28-specific monoclonal antibodies is capable of expanding regulatory T-cells and thereby specifically interferes with the pathogenesis of autoimmune diseases.

Application:
The monoclonal antibodies tested in this project are a promising therapeutic agent for a large number of autoimmune diseases.