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COLLOQUIUM PAPERS
Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines
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Department of Neuroimmunology, Max Planck Institute for Neurobiology, Am Klopferspitz, D-82152 Martinsried, Germany; and Institute for Clinical Neuroimmunology, Ludwig Maximilians University, Klinikum Grosshadern, Marchioninistrasse 15, D-81366 Munich, Germany
Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of multiple sclerosis (MS), and thus are logical targets for therapy. Indeed, several immunomodulatory agents, including IFN-
1b, IFN-1a, glatiramer acetate, and mitoxantrone, have had beneficial clinical effects in different forms of MS. However, because the available treatments are only partially effective, MS therapy needs to be further improved. Selective (antigen-specific) immunotherapies are especially appealing because in theory they combine maximal efficacy with minimal side effects. Indeed, several innovative immunotherapies have been successfully applied in experimental autoimmune encephalomyelitis. For example, autoreactive T cells can be selectively targeted by means of antigen, T cell receptor, or activation markers. However, experimental autoimmune encephalomyelitis is far from being a perfect approximation of MS because MS is more heterogeneous and the target antigen(s) is (are) not known. Further advances in MS therapy will depend on our growing understanding of the pathogenesis of this still incurable disease.
Abbreviations: APC, antigen-presenting cell; APL, altered peptide ligand; CDR, complementarity-determining region; EAE, experimental autoimmune encephalomyelitis; GA, glatiramer acetate; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; TCR, T cell receptor; TH, T helper.
To whom correspondence should be addressed. E-mail: reinhard.hohlfeld{at}med.uni-muenchen.de.
© 2004 by The National Academy of Sciences of the USA
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