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Title

Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model

Authors
Ochsendorf, Falk Rudiger
Noll, S.
Urban, M.
Popp, A.
Waldherr, D.
Haunschild, J.
Litzenburger, T.
Published in British Journal of Dermatology. 2005, vol. 153, no. 4, p. 758-766
Abstract BACKGROUND: Psoriasis is considered as a chronic immune-mediated disease characterized by inflammation and proliferation of the epidermis. OBJECTIVES: Targeting intercellular adhesion molecule 1 (ICAM-1) is an attractive therapeutic option as this molecule is critically involved in leucocyte adhesion and extravasation as well as in lymphocyte activation. METHODS: We have selected the fully human monoclonal antibody MOR102 (#5) against ICAM-1 from the Human Combinatorial Antibody Library (HuCAL). This antibody, as human IgG4 [corrected] was tested for its ability to interfere with lymphocyte activation and adhesion in vitro as well as for its antipsoriatic efficacy in vivo using the psoriasis-severe combined immunodeficient (SCID) mouse model. RESULTS: The antibody demonstrated efficient inhibition of lymphocyte adhesion to ICAM-1 in vitro, with an IC(50) of approximately 0.4 microg mL(-1) (3 nmol L(-1)). In addition, MOR102 (#5) reduced lymphocyte proliferation in mixed lymphocyte cultures by approximately 50%. The in vivo efficacy of MOR102 (#5) was tested on grafts derived from lesional skin of patients with chronic plaque-stage psoriasis transplanted on to SCID mice. Intraperitoneal injection of 10 mg kg(-1) of MOR102 (#5) antibody every alternate day over a period of 4 weeks resulted in reconstitution of orthokeratotic differentiation and a significant (P < 0.05) reduction in epidermal thickness as well as marked reduction in the inflammatory infiltrate. Therapeutic activity may be related to the targeting of ICAM-1 on keratinocytes and thus preventing efficient activation of local T cells. CONCLUSIONS: Based on the efficacy of the fully human monoclonal antibody MOR102 (#5) shown in vitro as well as in vivo in the psoriasis-SCID mouse model, initiation of clinical studies is indicated.
Keywords AnimalsAntibodies, Monoclonal/immunology/*therapeutic useCell Adhesion/immunologyCell ProliferationCells, CulturedEpidermis/pathologyHumansIntercellular Adhesion Molecule-1/*immunologyLymphocyte Activation/immunologyLymphocyte Culture Test, MixedMiceMice, SCIDPsoriasis/immunology/pathology/*therapySkin Transplantation
Identifiers
PMID: 16181457
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BOEHNCKE, Wolf-Henning et al. Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model. In: British Journal of Dermatology, 2005, vol. 153, n° 4, p. 758-766. https://archive-ouverte.unige.ch/unige:29794

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Deposited on : 2013-09-20

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