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. 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(R)). This antibodies human 94 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 IC50 of similar to 0.4 mu g mL(-1) (3 nmol L-1). In addition, MOR102 (#5) reduced lymphocyte proliferation in mixed lymphocyte cultures by similar to 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.