Therapeutic principles of monoclonal antibodies

Chronic inflammation represents the key pathogenic event of many diseases, autoimmune rheumatic diseases, such as psoriasis, inflammatory bowel diseases, asthma, multiple sclerosis, atherosclerosis, and others. Conventional therapies for many of these disorders do not lead to the resolution of the inflammatory disorder and are frequently associated with limited effectiveness and severe side effects.

Professor Joachim R. Kalden, Member of the Department for Molecular Immunology, Nikolaus-Fiebiger-Zentrum, University Medical School Erlangen-Nuremberg, presents therapeutic principles based on monoclonal antibodies.

"New therapeutic strategies had to be developed as based on our progressive knowledge of pathogenic mechanisms involved in different chronic inflammatory disease entities", says Kalden, who is also the former Director of the Department of Internal Medicine 3 (Rheumatology and Clinical Immunology) of the University Medical School Erlangen-Nuremberg.

Most of the progress made over the past years for the treatment of chronic inflammatory and autoimmune diseases is based on a method for the preparation of monoclonal antibodies on a large scale, as published 1975 by Köhler, Milstein and Jerne, who won the Nobel Prize in 1984. Today, therapeutic antibodies are essential assets for physicians fighting cancer, inflammation and infections.

Diseases where the medication with monoclonal antibodies have significantly changed our treatment options for patients are autoimmune rheumatic diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, psoriasis and chronic inflammatory bowel diseases such as Crohn's disease. Using monoclonal antibodies or fusion proteins in quite a number of these diseases it was demonstrated not only to block the chronic, progressive tissue destructive inflammatory process and to achieve low disease activity but also in some situations to achieve a remission. Before the introduction of these new treatment principles most of these diseases led very early to a disabling status of the patient combined with disability to continue to work, leading to unemployment.

The major targets for the therapeutic monoclonal antibodies are proinflammatory cytokines such as tumour necrosis factor alpha and interleukin-12/interleukin-23. More recently it has also been demonstrated that targeting B- or T cells might be efficacious in treating chronic inflammatory diseases.

Since, with this new medications, only up to 70% of patients will benefit and partly only to a limited extend, it is necessary to develop new and maybe even more specific medications. These new approaches include the interference with intracellular signalling mechanisms, the definition of new molecules such as cytokines and chemokines and B- and T cells not only as targets but also with regard to their immunomodulating capacity such as regulatory T cells.

"Specifically, the introduction of monoclonal antibodies in the treatment of chronic inflammatory diseases is an outstanding example, how results obtained by basic science might be translated into clinical application", says Kalden.

Beside a symposium co-organized by the National Academy of Science Leopoldina and EFIS new aspects of immune intervention will be discussed in a variety of workshops and symposia during this conference. Hopefully new and efficacious therapeutic strategies will come up not only for chronic inflammatory diseases but also for cancers, specifically lymphomas and leukemias, and disease entities such as asthma and sepsis.

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