Literature DB >> 29678878

A bispecific antibody that targets IL-6 receptor and IL-17A for the potential therapy of patients with autoimmune and inflammatory diseases.

Michael Lyman1, Vincent Lieuw1, Robyn Richardson1, Anjuli Timmer1, Christine Stewart1, Steve Granger1, Richard Woods2, Michela Silacci2, Dragan Grabulovski2, Roland Newman3.   

Abstract

Despite the success of current biological therapeutics for rheumatoid arthritis, these therapies, targeting individual cytokines or pathways, produce beneficial responses in only about half of patients. Therefore, better therapeutics are needed. IL-6 and IL-17A are proinflammatory cytokines in many autoimmune and inflammatory diseases, and several therapeutics have been developed to specifically inhibit them. However, targeting both of these cytokines with a bispecific therapeutic agent could account for their nonoverlapping proinflammatory functions and for the fact that IL-6 and IL-17A act in a positive feedback loop. Here, we present the development of MT-6194, a bispecific antibody targeting both IL-6R and IL-17A that was developed with the FynomAb technology. We also present data from mouse inflammatory disease experiments, indicating that simultaneous inhibition of both IL-6 and IL-17A yields enhanced efficacy compared with inhibition of each cytokine alone.
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Entities:  

Keywords:  antibody; antibody engineering; autoimmune disease; cytokine; inflammation

Mesh:

Substances:

Year:  2018        PMID: 29678878      PMCID: PMC6005441          DOI: 10.1074/jbc.M117.818559

Source DB:  PubMed          Journal:  J Biol Chem        ISSN: 0021-9258            Impact factor:   5.157


  36 in total

1.  The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses.

Authors:  D Aletaha; J S Smolen
Journal:  Rheumatology (Oxford)       Date:  2002-12       Impact factor: 7.580

2.  Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group.

Authors:  P E Lipsky; D M van der Heijde; E W St Clair; D E Furst; F C Breedveld; J R Kalden; J S Smolen; M Weisman; P Emery; M Feldmann; G R Harriman; R N Maini
Journal:  N Engl J Med       Date:  2000-11-30       Impact factor: 91.245

3.  A bispecific HER2-targeting FynomAb with superior antitumor activity and novel mode of action.

Authors:  Simon Brack; Isabella Attinger-Toller; Babette Schade; Frédéric Mourlane; Kristina Klupsch; Richard Woods; Helen Hachemi; Ulrike von der Bey; Susann Koenig-Friedrich; Julian Bertschinger; Dragan Grabulovski
Journal:  Mol Cancer Ther       Date:  2014-07-03       Impact factor: 6.261

4.  Interleukin 17A acts synergistically with interferon γ to promote protection against Leishmania infantum infection.

Authors:  Manuela Sales Lima Nascimento; Vanessa Carregaro; Djalma Souza Lima-Júnior; Diego Luís Costa; Bernhard Ryffel; Malcolm S Duthie; Amélia de Jesus; Roque Pacheco de Almeida; João Santana da Silva
Journal:  J Infect Dis       Date:  2014-10-01       Impact factor: 5.226

5.  Synergistic effects of interleukin-1β and interleukin-17A antibodies on collagen-induced arthritis mouse model.

Authors:  Yu Zhang; Guiping Ren; Mo Guo; Xianlong Ye; Jingzhuang Zhao; Liming Xu; Jianying Qi; Fangming Kan; Miao Liu; Deshan Li
Journal:  Int Immunopharmacol       Date:  2012-12-29       Impact factor: 4.932

6.  Immunogenicity of tocilizumab in patients with rheumatoid arthritis.

Authors:  Johanna Sigaux; Moustafa Hamze; Claire Daien; Jacques Morel; Roman Krzysiek; Marc Pallardy; Bernard Maillere; Xavier Mariette; Corinne Miceli-Richard
Journal:  Joint Bone Spine       Date:  2016-06-28       Impact factor: 4.929

Review 7.  Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis.

Authors:  T Pincus; Y Yazici; T Sokka; D Aletaha; J S Smolen
Journal:  Clin Exp Rheumatol       Date:  2003 Sep-Oct       Impact factor: 4.473

8.  Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial.

Authors:  Michael E Weinblatt; Edward C Keystone; Daniel E Furst; Larry W Moreland; Michael H Weisman; Charles A Birbara; Leah A Teoh; Steven A Fischkoff; Elliot K Chartash
Journal:  Arthritis Rheum       Date:  2003-01

9.  Discovery and characterization of COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor for the treatment of inflammatory diseases.

Authors:  Michela Silacci; Wibke Lembke; Richard Woods; Isabella Attinger-Toller; Nadja Baenziger-Tobler; Sarah Batey; Roger Santimaria; Ulrike von der Bey; Susann Koenig-Friedrich; Wenjuan Zha; Bernd Schlereth; Mathias Locher; Julian Bertschinger; Dragan Grabulovski
Journal:  MAbs       Date:  2015-09-22       Impact factor: 5.857

Review 10.  Interleukin 6 and rheumatoid arthritis.

Authors:  Yuji Yoshida; Toshio Tanaka
Journal:  Biomed Res Int       Date:  2014-01-12       Impact factor: 3.411

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  5 in total

Review 1.  IL-6: a cytokine at the crossroads of autoimmunity.

Authors:  Britta E Jones; Megan D Maerz; Jane H Buckner
Journal:  Curr Opin Immunol       Date:  2018-09-21       Impact factor: 7.486

Review 2.  Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow.

Authors:  Raoufeh Ahamadi-Fesharaki; Abolfazl Fateh; Farzam Vaziri; Ghasem Solgi; Seyed Davar Siadat; Fereidoun Mahboudi; Fatemeh Rahimi-Jamnani
Journal:  Mol Ther Oncolytics       Date:  2019-03-23       Impact factor: 7.200

3.  Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective.

Authors:  Pascale Zwicky; Susanne Unger; Burkhard Becher
Journal:  J Exp Med       Date:  2020-01-06       Impact factor: 14.307

Review 4.  Bioassay Development for Bispecific Antibodies-Challenges and Opportunities.

Authors:  Ames C Register; Somayeh S Tarighat; Ho Young Lee
Journal:  Int J Mol Sci       Date:  2021-05-19       Impact factor: 5.923

Review 5.  A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target.

Authors:  Bingyi Yang; Ming Zhao; Haijing Wu; Qianjin Lu
Journal:  Front Immunol       Date:  2020-10-02       Impact factor: 7.561

  5 in total

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