Protection of marmoset monkeys against EAE by treatment with a murine antibody blocking CD40 (mu5D12)

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Laman, J.D.

Hart, B.A. 't

Brok, H.

Meurs, M. van

Schellekens, M.M.

Kasran, A.

Boon, L.

Bauer, J.

Boer, M. de

Ceuppens, J.
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. Chemicals/CAS: Antibodies, Monoclonal; Antigens, CD40
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AutoimmunityCD40Dendritic cellImmunotherapyMultiple sclerosisCD40 ligand monoclonal antibodymonoclonal antibody mu5D12unclassified drugallergic encephalomyelitisanimal cellanimal experimentanimal modelanimal tissueantigen functionantigen presenting cellcell functionchronic inflammationclinical featurecontrolled studydemyelinating diseasedisease coursedrug activitydrug distributiondrug efficacyeffector cellhumanhuman cellinflammationlymphocyte activationlymphoid organmonkeymultiple sclerosisnonhumannuclear magnetic resonance imagingoutbred strainpriority journalwhite matterAnimalsAntibodies, MonoclonalAntigens, CD40CallithrixCross ReactionsEncephalomyelitis, Autoimmune, ExperimentalFemaleMaleMice
TNO Identifier
236627
Repository link
ISSN
00142980
Source
European Journal of Immunology, 32(8), pp. 2218-2228.
Pages
2218-2228
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