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Therapeutic advances in rheumatology with the use of recombinant proteins

Nature Clinical Practice Rheumatology volume 4, pages 605–614 (2008)Cite this article

Abstract

Antibody engineering and protein design have led to the creation of a new era of targeted anti-inflammatory therapies in rheumatology. Recombinant DNA technologies have enabled the selection and humanization of specific antibody fragments in order to develop therapeutic reagents of any specificity that can be 'armed' to deliver effective anti-inflammatory 'payloads'. Antibodies and antibody-like proteins provide the opportunity to block key soluble mediators of inflammation in their milieu, or alternatively to block intracellular inflammation-triggering pathways by binding to an upstream cell-surface receptor. These designer proteins can be tuned for desired pharmacokinetic and pharmacodynamic effects, and represent tools for specific therapeutic intervention by delivering precisely the required immunosuppressive effect. The extent of desired and undesired effects of a particular biologic therapy, however, can be broader than initially predicted and require careful evaluation during clinical trials. This Review highlights advances in recombinant technologies for the development of novel biologic therapies in rheumatology.

Key Points

  • Led by the successful wave of anti-inflammatory modulators in rheumatic disease therapy, designed protein therapeutic agents now outnumber and surpass the number of small-molecule drugs approved annually by the FDA

  • Antibodies and immunoadhesins that directly target cytokines for their systemic removal (ligand ablation; e.g. adalinmumab, infliximab) have become effective therapeutic strategies in rheumatology

  • Novel and powerful protein display technologies have enabled the rapid isolation of fully human therapeutics, often with unique disease-targeting specificities

  • Engineered antibodies have become essential therapies against a range of rheumatic diseases, and future product designs will offer enhanced clinical efficacy with fewer adverse events

  • By incorporating our in-depth knowledge of protein structure, the future impact of novel engineered biologic agents as treatments for rheumatic diseases will be immense

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Figure 1: Approved or in-trial antibody-based and receptor-based biologic agents (in red) targeting either primary cells (B cells, T cells, macrophages, endothelial cells, osteoclasts and fibroblasts) and/or the circulating mediators (TNF, IL-15, VEGF, RANKL, BLyS, CD80/CD86) involved in rheumatic diseases.
Figure 2: Structural comparisons of engineered, targeted immunomodulators.

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Acknowledgements

A Rothe is supported by Deutsche Krebshilfe and the Köln Fortune Foundation/Germany whilst working at the Commonwealth Scientific and Industrial Research Organisation (CSIRO). In addition, we acknowledge our scientific colleagues in our three primary institutions with whom we have enjoyed many exciting discussions on the new wave of therapeutic anti-inflammatory proteins.

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Authors and Affiliations

  1. A Rothe is a Medical Scientist in the Department of Internal Medicine at the University Hospital of Cologne, Cologne, Germany.,

    Achim Rothe

  2. BE Power is Head of Recombinant Technologies at Patrys Ltd, Melbourne.,

    Barbara E Power

  3. PJ Hudson is CEO of AviPep Pty Ltd and a Director of AntibOZ Pty Ltd, Melbourne, Vic, Australia.,

    Peter J Hudson

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  1. Achim Rothe
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  2. Barbara E Power
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  3. Peter J Hudson
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Correspondence to Achim Rothe.

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Competing interests

BE Power is an employee and stockholder in Patrys Ltd. PJ Hudson and BE Power are both founding Directors and stockholders in AntibOZ Pty Ltd and PJ Hudson is CEO and a stockholder in AviPep Pty Ltd.

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Rothe, A., Power, B. & Hudson, P. Therapeutic advances in rheumatology with the use of recombinant proteins. Nat Rev Rheumatol 4, 605–614 (2008). https://doi.org/10.1038/ncprheum0909

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