Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model.
BACKGROUND
Psoriasis is considered as a chronic immune-mediated disease characterized by inflammation and proliferation of the epidermis.


OBJECTIVE
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.
Boehncke
W-H
WH
Department of Dermatology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany MorphoSys AG, Lena-Christ-Strasse 48, 82152 Martinsried, Germany.
Ochsendorf
F R
FR
Noll
S
S
Urban
M
M
Popp
A
A
Waldherr
D
D
Haunschild
J
J
Litzenburger
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004817:Epidermis / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016038:Skin Transplantation
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1