title: ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model.
abstract: BACKGROUND
  The anti-human Fas/APO-1/CD95 (Fas) mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098) targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg) were investigated to examine the potential of ARG098 as a therapy for RA.
  
  
  METHODS
  ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model.
  
  
  RESULTS
  ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model.
  
  
  CONCLUSIONS
  ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA.
authors.affiliation: Research & Development Center, Santen Pharmaceutical Co,, Ltd,, 8916-16, Takayama-cho, Ikoma-shi, Nara, Japan. noriko.odani@santen.co.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Odani-Kawabata
authors.forename: Miwa
authors.initials: M
authors.lastname: Takai-Imamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Katsuta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Keiko
authors.initials: K
authors.lastname: Funahashi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsubara
authors.forename: Minoru
authors.initials: M
authors.lastname: Sasano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aono
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D002357:Cartilage Diseases / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use*; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D019014:fas Receptor