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Monoclonal Antibodies Can Protect L–Asparaginase Against Inactivation by Trypsin

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Abstract

We show that a non–inhibitory monoclonal antibody (MAB) can be selected that provides substantial and sustained protection against proteolytic inactivation of L–aspar aginase by trypsin. Of six non–inhibitory, high affinity, monoclonal antibodies to L–asparaginase, one afforded approximately 70% protection. Inactivation of L–asparaginase is associated with a single cleavage adjacent to lysine–29 that results in loss of an N–terminal fragment with a calculated MW of 2,647. The protective MAB prevented this trypsin cleavage. The products of gene fusions of “humanized” fragments of such antibodies and L–asparaginase could have increased clinical utility.

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Author notes

  1. E. Y. Shami: Corresponding author.

Authors and Affiliations

  1. Hybrisens Ltd. York University Campus, Farq. Bldg. ♯104, 4700 Keele St., Toronto, Ontario, M3J-1P3, Canada

    M. Ramjeesingh, M. Zywulko, A. Rothstein & E. Y. Shami

  2. Dept. of Medical Biophysics, University of Toronto,

    A. Rothstein

  3. Dept. of Biology, York University, Toronto

    E. Y. Shami

Authors
  1. M. Ramjeesingh
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  2. M. Zywulko
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  3. A. Rothstein
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  4. E. Y. Shami
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Ramjeesingh, M., Zywulko, M., Rothstein, A. et al. Monoclonal Antibodies Can Protect L–Asparaginase Against Inactivation by Trypsin. Nat Biotechnol 10, 442–445 (1992). https://doi.org/10.1038/nbt0492-442

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  • DOI: https://doi.org/10.1038/nbt0492-442

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