FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model

Abstract

In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg-1 doses. Groups treated with doses of 10 and 3 mg kg-1had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2±59.6 to 231.4±40.4 μm (P<0.005) in the 10-mg kg-1 group, and from 323.4±69.6 to 237.5±73.6 μm in the 3-mg kg-1 group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases. © 2008 The Society for Investigative Dermatology.