Protection of marmoset monkeys against EAE by treatment with a murine antibody blocking CD40 (mu5D12).
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.
Laman
Jon D
JD
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. Laman@immu.fgg.eur.nl
't Hart
Bert A
BA
Brok
Herbert
H
Meurs
Marjan van
Mv
Schellekens
Marc M
MM
Kasran
Ahmad
A
Boon
Louis
L
Bauer
Jan
J
Boer
Mark de
Md
Ceuppens
Jan
J
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
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens