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Scientific article
English

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

Published inBritish journal of dermatology, vol. 153, no. 4, p. 758-766
Publication date2005
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
  • Animals
  • Antibodies, Monoclonal/immunology/*therapeutic use
  • Cell Adhesion/immunology
  • Cell Proliferation
  • Cells, Cultured
  • Epidermis/pathology
  • Humans
  • Intercellular Adhesion Molecule-1/*immunology
  • Lymphocyte Activation/immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, SCID
  • Psoriasis/immunology/pathology/*therapy
  • Skin Transplantation
Affiliation Not a UNIGE publication
Citation (ISO format)
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. doi: 10.1111/j.1365-2133.2005.06657.x
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ISSN of the journal0007-0963
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