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Monoclonal Antibodies: Past, Present and Future

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Concepts and Principles of Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 260))

Abstract

Monoclonal antibodies (mAbs) are immunoglobulins designed to target a specific epitope on an antigen. Immunoglobulins of identical amino-acid sequence were originally produced by hybridomas grown in culture and, subsequently, by recombinant DNA technology using mammalian cell expression systems. The antigen-binding region of the mAb is formed by the variable domains of the heavy and light chains and contains the complementarity-determining region that imparts the high specificity for the target antigen. The pharmacokinetics of mAbs involves target-mediated and non-target-related factors that influence their disposition.

Preclinical safety evaluation of mAbs differs substantially from that of small molecular (chemical) entities. Immunogenicity of mAbs has implications for their pharmacokinetics and safety. Early studies of mAbs in humans require careful consideration of the most suitable study population, route/s of administration, starting dose, study design and the potential difference in pharmacokinetics in healthy subjects compared to patients expressing the target antigen.

Of the ever-increasing diversity of therapeutic indications for mAbs, we have concentrated on two that have proved dramatically successful. The contribution that mAbs have made to the treatment of inflammatory conditions, in particular arthritides and inflammatory bowel disease, has been nothing short of revolutionary. Their benefit has also been striking in the treatment of solid tumours and, most recently, as immunotherapy for a wide variety of cancers. Finally, we speculate on the future with various new approaches to the development of therapeutic antibodies.

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Authors and Affiliations

  1. JPC PharMed Ltd , Kent, UK

    J. Posner

  2. King’s College London, London, UK

    J. Posner

  3. Transcrip Partners, Reading, UK

    P. Barrington

  4. Kings Health Partners, London, UK

    T. Brier

  5. Guy’s and St Thomas’ NHS Foundation Trust, London, UK

    T. Brier

  6. AstraZeneca, Cambridge, UK

    T. Brier

  7. Eli-Lilly and Company, Indianapolis, IN, USA

    A. Datta-Mannan

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  1. J. Posner
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  2. P. Barrington
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  3. T. Brier
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  4. A. Datta-Mannan
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Editors and Affiliations

  1. Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

    James E. Barrett

  2. Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King’s College London, London, UK

    Clive P. Page

  3. Department of Pharmacology, Johannes Gutenberg University, Mainz, Rheinland-Pfalz, Germany

    Martin C. Michel

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Posner, J., Barrington, P., Brier, T., Datta-Mannan, A. (2019). Monoclonal Antibodies: Past, Present and Future. In: Barrett, J., Page, C., Michel, M. (eds) Concepts and Principles of Pharmacology. Handbook of Experimental Pharmacology, vol 260. Springer, Cham. https://doi.org/10.1007/164_2019_323

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