title: 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(-1) had 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 microm (P<0.005) in the 10-mg kg(-1) group, and from 323.4+/-69.6 to 237.5+/-73.6 microm 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.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. sraychaudhuri@ucdavis.edu
authors.forename: Siba P
authors.initials: SP
authors.lastname: Raychaudhuri
authors.forename: Smriti
authors.initials: S
authors.lastname: Kundu-Raychaudhuri
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Taro
authors.initials: T
authors.lastname: Masunaga
authors.forename: Kaori
authors.initials: K
authors.lastname: Kubo
authors.forename: Kaori
authors.initials: K
authors.lastname: Hanaoka
authors.forename: Wen-Yue
authors.initials: WY
authors.lastname: Jiang
authors.forename: Leonore A
authors.initials: LA
authors.lastname: Herzenberg
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Herzenberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018106:CD28 Antigens / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D014183:Transplantation, Heterologous / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018106:CD28 Antigens; C530729:FR255734; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine