title: A Humanized Monoclonal Antibody against Heat Shock Protein 60 Suppresses Murine Arthritis and Colitis and Skews the Cytokine Balance toward an Anti-Inflammatory Response.
abstract: We have previously shown that naturally occurring as well as acquired Abs against the Mycobacterium tuberculosis heat shock protein (HSP)65 protect against the induction of murine autoimmune inflammatory arthritis. In the present work, we have studied the anti-inflammatory effect of prozumab, a humanized anti-HSP mAb in murine inflammatory arthritis and colitis, and its effects on cytokine secretion. Prozumab was shown to bind to HSP60, the highly conserved mammalian homolog of the bacterial protein, and it was found to be effective in protecting and suppressing autoimmune arthritis in the models of adjuvant arthritis and collagen-induced arthritis in rats and mice, respectively, as well as in acute hapten-mediated colitis and chronic, spontaneous colitis models. Mechanistically, prozumab induces IL-10 secretion from naive human PBMCs and suppresses the secretion of IFN-γ and IL-6 from anti-CD3-activated human PBMCs. These findings make prozumab a promising potential drug for treating human rheumatoid arthritis and inflammatory bowel disease, as well as a wide range of autoimmune inflammatory diseases.
authors.affiliation: Department of Medicine, Hadassah University Hospital, Jerusalem 91120, Israel; and.
authors.forename: Rina
authors.initials: R
authors.lastname: Ulmansky
authors.affiliation: ProtAb Ltd., Jerusalem 91120, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Landstein
authors.affiliation: Department of Medicine, Hadassah University Hospital, Jerusalem 91120, Israel; and.
authors.forename: Eli
authors.initials: E
authors.lastname: Moallem
authors.affiliation: ProtAb Ltd., Jerusalem 91120, Israel.
authors.forename: Virginie
authors.initials: V
authors.lastname: Loeb
authors.affiliation: Department of Medicine, Hadassah University Hospital, Jerusalem 91120, Israel; and.
authors.forename: Avi
authors.initials: A
authors.lastname: Levin
authors.affiliation: ProtAb Ltd., Jerusalem 91120, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Meyuhas
authors.affiliation: ProtAb Ltd., Jerusalem 91120, Israel.
authors.forename: Galia
authors.initials: G
authors.lastname: Katzavian
authors.affiliation: ProtAb Ltd., Jerusalem 91120, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Yair
authors.affiliation: Department of Medicine, Hadassah University Hospital, Jerusalem 91120, Israel; and ProtAb Ltd., Jerusalem 91120, Israel yakovn@hadassah.org.il.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Naparstek
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001426:Bacterial Proteins / Q000276:immunology; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001426:Bacterial Proteins; D018834:Chaperonin 60; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D007371:Interferon-gamma