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Modulating the pharmacokinetics of therapeutic antibodies

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Abstract

With the advent of antibody fragments and alternative binding scaffolds, that are devoid of Fc-regions, strategies to increase the half-life of small proteins are becoming increasingly important. Currently, the established method is chemical PEGylation, but more elaborate approaches are being described such as polysialylation, amino acid polymers and albumin-binding derivatives. This article reviews the main strategies for pharmacokinetic enhancement, primarily chemical conjugates and recombinant fusions that increase apparent molecular weight or hydrodynamic radius or interact with serum albumin which itself has a long plasma half-life. We highlight the key chemical linkage methods that preserve antibody function and retain stability and look forward to the next generation of technologies which promise to make better quality pharmaceuticals with lower side effects. Although restricted to antibodies, all of the approaches covered can be applied to other biotherapeutics.

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Acknowledgements

The authors acknowledge funding from Imperial College, Cancer Research UK (Ref: C18960) and European Union FP6 (Immuno-PDT Ref: LSHC-CT-2006-037489) which fund MPD, AC and CC respectively. We thank David Leak for critically reading the manuscript.

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  1. Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, Exhibition Road, London, SW7 2AZ, UK

    A. Constantinou, C. Chen & M. P. Deonarain

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  1. A. Constantinou
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Correspondence to M. P. Deonarain.

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Constantinou, A., Chen, C. & Deonarain, M.P. Modulating the pharmacokinetics of therapeutic antibodies. Biotechnol Lett 32, 609–622 (2010). https://doi.org/10.1007/s10529-010-0214-z

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