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Monoclonal Antibodies and Antibody-Based Biotherapeutics in Inflammatory Diseases

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Pharmaceutical Biotechnology

Abstract

Immune-mediated inflammatory diseases encompass a broad and diverse spectrum of serious chronic disorders, many of which have significant need for safe and effective pharmacotherapies. The classes of conventional drugs used to treat immune-mediated inflammatory diseases include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, sulfasalazine, 5-aminosalicylates, methotrexate, azathioprine, and 6-mercaptopurine; however, in many instances, these agents have exhibited limited efficacy or are associated with significant serious on-target and off-target side effects. The initial rationale and promise of complex biologics, such as monoclonal antibodies (mAbs), as pharmacotherapy was focused on oncology and organ transplantation (Ehrlich 1891; Gura 2002); however, recent decades have witnessed the successful development of a number of complex biologics as both anti-allergic and anti-inflammatory therapies. Five of the top-selling mAbs are for the treatment of chronic inflammatory conditions, and this area of research and development is rapidly expanding. Complex biologics are a subclass of protein therapeutics. They are large molecular weight glycoproteins designed and produced through recombinant DNA technology and require production in eukaryotic cells using bioreactor technology. These modalities have provided many targeted and efficacious therapeutic options for patients and are providing significant insights into the underlying complex pathological processes of these disorders, which, in turn, are identifying new targets for treatment of these diseases. A significant translational insight derived from the clinical development programs of complex biologic pharmacotherapy is the dysregulation of common proinflammatory mediators, such as tumor necrosis factor alpha (TNFα), across diverse rheumatologic, dermatologic, and gastroenterologic pathologies. In addition, the observation of patient subsets within a disease that are refractory to a particular therapy indicates that dysregulation of different mediators can drive the underlying pathological processes within a disease.

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Acknowledgement 

The authors would like to express their gratitude to the critical review of Dr. Karen Weiss and editorial support of Dr. Kenneth Graham of Janssen Research and Development, LLC of Johnson & Johnson.

Author information

Authors and Affiliations

  1. Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA

    Honghui Zhou Ph.D. & Zhenhua Xu Ph.D.

  2. Department of Clinical Pharmacology and Pharmacokinetics, Shire, Lexington, MA, USA

    Mary Ann Mascelli Ph.D.

  3. Biologics Clinical Pharmacology, Janssen Research & Development, LLC, Radnor, PA, USA

    Hugh M. Davis Ph.D.

Authors
  1. Honghui Zhou Ph.D.
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  2. Zhenhua Xu Ph.D.
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  3. Mary Ann Mascelli Ph.D.
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  4. Hugh M. Davis Ph.D.
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Corresponding author

Correspondence to Honghui Zhou Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Utrecht University, Utrecht, Utrecht, The Netherlands

    Daan J. A. Crommelin

  2. Department of Pharmaceutical Sciences and Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada

    Robert D. Sindelar

  3. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, College of Pharmacy, Memphis, Tennessee, USA

    Bernd Meibohm

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Zhou, H., Xu, Z., Mascelli, M.A., Davis, H.M. (2013). Monoclonal Antibodies and Antibody-Based Biotherapeutics in Inflammatory Diseases. In: Crommelin, D., Sindelar, R., Meibohm, B. (eds) Pharmaceutical Biotechnology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6486-0_20

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