CD-5: T Regulatory Cell-targeted Therapy Using Low-dose IL-2

Coordinators: Prof. K. F. Rabe, Prof. G. Riemekasten, Prof. S. Schreiber, Prof. S. Weidinger, Prof. D. Zillikens

In CD-5 a randomized, placebo-controlled, clinical “proof-of concept” study (Phase 2a) is conducted to investigate the safety and clinical efficacy of low-dose therapy with the cytokine interleukin-2 (IL-2) in five different chronic inflammatory diseases from the fields of dermatology (atopic dermatitis, pemphigus vulgaris, mucous membrane pemphigoid), gastroenterology (ulcerative colitis) and rheumatology (polymyositis/dermatomyositis). In cooperation with the RTFs, the clinical study will be accompanied by an extensive scientific program aimed at gaining new insights into the pathomechanisms of these diseases as well as the mechanisms of action of low-dose IL-2 therapy.

What does this research area's work build on?

Low-dose IL-2 therapy induces the selective expansion of regulatory T cells (Treg), which are indispensable for the suppression of excessive immune responses and for the control inflammatory processes.  The restoration or strengthening of Treg acitivity may alleviate the clinical symptoms of inflammatory and immunological diseases. First phase 1 and 2 clinical studies, some of which were carried out by cluster members, were able to prove the safety and very good tolerance of low-dose IL-2 therapy in patients with different inflammatory and immunological diseases, such as systemic lupus erythematosus (SLE), and to provide preliminary evidence for the clinical efficacy of this treatment.

 

What are the main research objectives?

The main aim of this clinical study is to use a standardized master protocol to investigate and compare the safety and efficacy of low-dose IL-2 therapy in patients with different chronic inflammatory diseases in order to create the scientific basis for more comprehensive studies (what is known as a “disease-finding basket trial”). In addition to the detailed analyses of Treg sub-populations, the accompanying scientific investigations include extensive studies of relevant immune cells, cytokines and intracellular signaling pathways in order to gain decisive insights into both general as well as disease-specific modes of action of the treatment. Suitable biomarkers for the treatment response and follow-up checks are also to be identified and complex models are to be developed for predicting an individual treatment response.

 

What makes this research area special?

The concept of the low-dose IL-2 therapy was developed by participating scientists of CD-5 from animal model-based pre-clinical research through to clinical application. There is internationally recognized and leading German expertise in the field of low-dose IL-2 therapy of chronic inflammatory diseases. The clinical introduction of low-dose IL-2 therapy can therefore be regarded as a prime example of a successful “bench-to-bedside” approach within translational immunology and medicine.

 

What does the research area contribute to precision medicine in chronic inflammation?

Low-dose IL-2 therapy and its associated reconstitution and enhancement of immunological tolerance mechanisms interferes directly with the immunopathogenesis of many chronic inflammatory diseases and therefore represents a promising and selective biological treatment approach with a unique and physiological mode of action. The establishment of such a targeted approach would be an important advance in the treatment of numerous chronic inflammatory diseases for which there exist currently no specific or only inadequately effective treatment options.

 

Cooperation with other research areas in the cluster

Detailed phenotypic analyses of Treg sub-populations, including antigen specificity, TCR repertoire and epigenetic changes, are to be carried out in cooperation with RTF I, RTF VI, TI-2 and TI-4. The identification of biomarkers and development of models for the treatment response will be supported by RTF VIII by way of integrated analyses of proteomes, transcriptomes, epigenomes and metabolomes.

 

Members

Priv.-Doz. Dr. Konrad Aden

Full member

UKSH Campus Kiel
Department of Internal Medicine I

Prof. Dr. med. Thomas Bahmer

Full member

UKSH Campus Kiel
Department of Internal Medicine I

PD Dr. Katja Bieber

Associated member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology

Prof. Dr. Hauke Busch

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
System Biology of Inflammatory Diseases

Prof. Dr. Marc Ehlers

Full member

UKSH Campus Lübeck
Institute of Medical Nutrition Science
Immunology and Glycoanalytics

M.Sc. Melina Fonfara

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology, and Allergology
AG Prof. Emmert

Hanna Graßhoff

Associated member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology
AG Prof. Riemekasten

M.Sc. Jan Hartmann

Assoziiertes Mitglied

UKSH Campus Kiel
Klinik für Dermatologie, Venerologie und Allergologie
Quincke Forschungszentrum
AG Prof. Weidinger

Prof. Dr. med. Bimba Franziska Hoyer

Full member

UKSH Campus Kiel
Department of Internal Medicine I
Section Rheumatology

Dr. rer. nat. Matthias Hübenthal

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
AG Prof. Weidinger

Dr. med. Jens Humrich

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

Prof. Dr. Christoph Kaleta

Full member

UKSH Campus Kiel
Institute of Experimental Medicine
c/o Transfusion Medicine

Prof. Dr. Jörg Köhl

Full member

University of Lübeck
Institute for Systemic Inflammation Research

Prof. Dr. Inke König

Full member

University of Lübeck
Institute for Medical Biometrics and Statistics

Prof. Dr. Tanja Lange

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

Prof. Dr. Ralf Ludwig

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Model Systems of Inflammatory Skin Diseases

Prof. Dr. Rudolf Manz

Full member

University of Lübeck
Institute for Systemic Inflammation Research

Prof. Dr. Klaus F. Rabe

Full member

LungenClinic Grosshansdorf
Section Pneumology

Prof. Dr. Gabriela Riemekasten

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

Dr. Elke Rodríguez

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Christian Sadik

Full member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology
Innate immunity

Prof. Dr. rer. nat. Alexander Scheffold

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Dr. Enno Schmidt

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Translational Research

Prof. Dr. med. Stefan Schreiber

Spokesperson

Kiel University
Institute of Clinical Molecular Biology

Prof. Dr. Thomas Schwarz

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Dr. med. Dora Stölzl

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Diamant Thaçi

Full member

UKSH Campus Lübeck
Comprehensive Center for Inflammation Medicine (CCIM)

Dr. med. Nina van Beek

Associated member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Prof. Dr. Stephan Weidinger

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Detlef Zillikens

Full member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Dr. rer. nat. Henner Zirpel

Associated member

UKSH Campus Lübeck
Institute for Inflammation Medicine
AG Prof. Thaçi