title: Protection of marmoset monkeys against EAE by treatment with a murine antibody blocking CD40 (mu5D12).
abstract: CD40-CD40 ligand interactions are crucial to cognate interactions between T cells, B cells and antigen-presenting cells (APC), and contribute to non-antigen-specific effector functions of APC in inflammatory disorders. Here we demonstrate that functional blockade of CD40 with an antagonist mouse anti-human CD40 monoclonal antibody (mAb mu5D12) effectively prevents clinical expression of chronic demyelinating experimental autoimmune encephalomyelitis (EAE) in outbred marmoset monkeys, a preclinical model of multiple sclerosis. Anti-CD40 mAb interfered with development of clinical symptoms of marmoset EAE during the treatment period, even when treatment was started several weeks after T cell priming. Magnetic resonance imaging demonstrated inflammatory activity in the brain at initiation of antibody treatment, confirming that treatment interfered with the disease process. Access of therapeutic anti-CD40 to potential sites of action, the secondary lymphoid organs and the brain white matter lesions, was visualized in situ. The present data are the first to demonstrate the clinical potential of blocking APC and effector cell functions using murine antagonist anti-CD40 mAb in the treatment of chronic inflammatory diseases.
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. Laman@immu.fgg.eur.nl
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Bert A
authors.initials: BA
authors.lastname: 't Hart
authors.forename: Herbert
authors.initials: H
authors.lastname: Brok
authors.forename: Marjan van
authors.initials: Mv
authors.lastname: Meurs
authors.forename: Marc M
authors.initials: MM
authors.lastname: Schellekens
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kasran
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Mark de
authors.initials: Md
authors.lastname: Boer
authors.forename: Jan
authors.initials: J
authors.lastname: Ceuppens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000276:immunology* / Q000502:physiology; D002144:Callithrix; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D008297:Male; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens