title: A novel murine anti-human Fas mAb which mitigates lymphadenopathy without hepatotoxicity.
abstract: Defects in Fas-mediated apoptosis are implicated in autoimmune diseases including rheumatoid arthritis (RA). Although induction of Fas-mediated apoptosis could have therapeutic effects on these diseases, it might cause deleterious effects in liver as Fas ligand or an agonistic anti-murine Fas antibody Jo2 causes severe hepatic injury in mice. We report here on the interesting characteristics of the newly obtained anti-Fas mAb, HFE7A, which cross-reacts with the Fas molecules of various species ranging from human to mouse and mitigates autoimmune symptoms without hepatotoxicity in mice. The administration of HFE7A to mice induced apoptosis in the thymocytes, although administration of HFE7A to mice or to marmosets did not induce any sign of hepatitis. The effect of HFE7A on liver is different from that of anti-murine Fas antibody Jo2, which causes acute and lethal hepatic injury to mice. Administration of HFE7A reduced lymphadenopathy and abnormal T cells in MRL-gld/gld mice. HFE7A induced apoptosis in synovial cells prepared from RA patients. Surprisingly, HFE7A protected mice from fulminant hepatitis induced by Jo2. Therefore, HFE7A is a potential therapeutic antibody not only for autoimmune diseases including RA but also for fulminant hepatitis.
authors.affiliation: Biomedical Research Laboratories, Sankyo Co., Ltd, Tokyo 140-8710, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Yoshida-Kato
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuki
authors.forename: J
authors.initials: J
authors.lastname: Ohsumi
authors.forename: J
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Tani
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Shiraishi
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
authors.forename: S
authors.initials: S
authors.lastname: Yonehara
authors.forename: N
authors.initials: N
authors.lastname: Serizawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000096:biosynthesis / Q000737:chemistry / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002144:Callithrix; D002478:Cells, Cultured; D005260:Female; D006520:Hepatitis, Animal / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007116:Immunization, Passive; D008206:Lymphatic Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008251:Macaca; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D002679:Pan troglodytes; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor