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Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment

Nature Biotechnology volume 26, pages 901–908 (2008)Cite this article

Abstract

Lysosomal storage diseases are characterized by deficiencies in lysosomal enzymes, allowing accumulation of target substrate in cells and eventually causing cell death. Enzyme replacement therapy is the principal treatment for most of these diseases. However, these therapies are often complicated by immune responses to the enzymes, blocking efficacy and causing severe adverse outcomes by neutralizing product activity. It is thus crucial to understand the relationships between genetic mutations, endogenous residual enzyme proteins (cross-reactive immunologic material), development of neutralizing antibodies and their impact on clinical outcomes of lysosomal storage diseases. For patients in whom neutralizing antibodies may cause severe adverse clinical outcomes, it is paramount to develop tolerance inducing protocols to preclude, where predictable, or treat such life-threatening responses.

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Figure 1: Impact of neutralizing antibody on enzyme entry and activity in ERT.
Figure 2: Neutralization assays.

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Acknowledgements

The authors thank S. Kozlowski, M. Norcross and M. Shapiro for critical readings of the manuscript.

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Authors and Affiliations

  1. Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, NIH Building 29B, 8800 Rockville Pike, Bethesda, 20892, Maryland, USA

    Jinhai Wang, Gibbes Johnson, Susan Kirshner, Daniela Verthelyi, Elizabeth Shores & Amy Rosenberg

  2. Department of Laboratory Medicine, NIH Clinical Center, Bethesda, 20892, Maryland, USA

    Jay Lozier

  3. Division of Gastroenterology Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA, White Oak, Bldg. 22, 10903 New Hampshire Ave., Silver Spring, 20993, Maryland, USA

    Anne Pariser

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Wang, J., Lozier, J., Johnson, G. et al. Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment. Nat Biotechnol 26, 901–908 (2008). https://doi.org/10.1038/nbt.1484

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