Discovery and characterization of olokizumab A humanized antibody targeting interleukin-6 and neutralizing gp130-signaling

被引：67
作者：
Shaw, Stevan [1 ]
Bourne, Tim [1 ]
Meier, Chris [1 ]
Carrington, Bruce [1 ]
Gelinas, Rich [2 ]
Henry, Alistair [1 ]
Popplewell, Andrew [1 ]
Adams, Ralph [1 ]
Baker, Terry [1 ]
Rapecki, Steve [1 ]
Marshall, Diane [1 ]
Moore, Adrian [1 ]
Neale, Helen [1 ]
Lawson, Alastair [1 ]
机构：
[1] UCB Pharma, Slough, Berks, England
[2] Inst Syst Biol, Seattle, WA USA
来源：
MABS | 2014年 / 6卷 / 03期
关键词：
interleukin; 6; IL-6; antibody; site; 3; gp130; olokizumab; neutralization; structure; CONFORMATIONAL-CHANGE; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; PHASE-II; BLOCKADE; DISEASE; IL-6; TOCILIZUMAB; COMBINATION;
D O I：
10.4161/mabs.28612
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe the discovery and characterization of olokizumab, a humanized antibody to IL-6. Data from structural biology, cell biology and primate pharmacology demonstrate the therapeutic potential of targeting IL-6 at Site 3, blocking the interaction with the signaling co-receptor gp130.
引用
收藏
页码：773 / 781
页数：9
相关论文
共 55 条
  • [1] ENGINEERING ANTIBODIES FOR THERAPY
    ADAIR, JR
    [J]. IMMUNOLOGICAL REVIEWS, 1992, 130 : 5 - 40
  • [2] Interleukin-6: From identification of the cytokine to development of targeted treatments
    Assier, Eric
    Boissier, Marie-Christophe
    Dayer, Jean-Michel
    [J]. JOINT BONE SPINE, 2010, 77 (06) : 532 - 536
  • [3] Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation:: Evidence in Crohn disease and experimental colitis in vivo
    Atreya, R
    Mudter, J
    Finotto, S
    Müllberg, J
    Jostock, T
    Wirtz, S
    Schütz, M
    Bartsch, B
    Holtmann, M
    Becker, C
    Strand, D
    Czaja, J
    Schlaak, JF
    Lehr, HA
    Autschbach, F
    Schürmann, G
    Nishimoto, N
    Yoshizaki, K
    Ito, H
    Kishimoto, T
    Galle, PR
    Rose-John, S
    Neurath, MF
    [J]. NATURE MEDICINE, 2000, 6 (05) : 583 - 588
  • [4] A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities
    Babcook, JS
    Leslie, KB
    Olsen, OA
    Salmon, RA
    Schrader, JW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) : 7843 - 7848
  • [5] BOUND WATER-MOLECULES AND CONFORMATIONAL STABILIZATION HELP MEDIATE AN ANTIGEN-ANTIBODY ASSOCIATION
    BHAT, TN
    BENTLEY, GA
    BOULOT, G
    GREENE, MI
    TELLO, D
    DALLACQUA, W
    SOUCHON, H
    SCHWARZ, FP
    MARIUZZA, RA
    POLJAK, RJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (03) : 1089 - 1093
  • [6] Hexameric structure and assembly of the interleukin-6/IL-6 α-receptor/gp130 complex
    Boulanger, MJ
    Chow, DC
    Brevnova, EE
    Garcia, KC
    [J]. SCIENCE, 2003, 300 (5628) : 2101 - 2104
  • [7] Structural changes in a cryo-cooled protein crystal owing to radiation damage
    Burmeister, WP
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2000, 56 : 328 - 341
  • [8] Burmester GR, 2012, ARTHRITIS RHEUM-US, V64, pS1075
  • [9] THE USE OF ELISA FOR DETECTION OF THE ANTIBODY-INDUCED CONFORMATIONAL CHANGE IN A VIRAL PROTEIN AND ITS INTERMOLECULAR SPREAD
    CEPICA, A
    YASON, C
    RALLING, G
    [J]. JOURNAL OF VIROLOGICAL METHODS, 1990, 28 (01) : 1 - 14
  • [10] Therapeutic antibodies: successes, limitations and hopes for the future
    Chames, Patrick
    Van Regenmortel, Marc
    Weiss, Etienne
    Baty, Daniel
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2009, 157 (02) : 220 - 233
123456