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Development and Characterization of a Neutralizing Anti-idiotype Antibody Against Mirvetuximab for Analysis of Clinical Samples

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Abstract

Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which represents a potential new treatment for patients with ovarian and other FRα-positive cancers. Since patient immune responses to biological therapeutics may negatively affect drug efficacy and patient safety, regulatory authorities require rigorous monitoring of patient samples. Taking advantage of the immune system’s ability to generate highly specific antibodies, the field has turned to anti-idiotype antibodies as powerful tools for the development of sensitive and specific bioassays. Here, we report the generation and characterization of a highly specific neutralizing anti-idiotype antibody directed against M9346A, the antibody moiety of mirvetuximab soravtansine. The anti-idiotype antibody recognizes M9346A with double-digit picomolar affinity, competes with folate receptor antigen for binding to M9346A, and can be used to develop both anti-drug-antibody and neutralizing antibody assays.

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Authors and Affiliations

  1. BioAnalytical Sciences, ImmunoGen, Inc., 830 Winter Street, Waltham, Massachusetts, 02453, USA

    Sven Loebrich, Mingfang Shen, Erika Cohen, Gillian Payne & Yiwei Zhao

  2. Antibody Production and Purification, ImmunoGen, 830 Winter Street, Waltham, Massachusetts, 02453, USA

    Ying Chen

  3. Analytical and Pharmaceutical Sciences, ImmunoGen, 830 Winter Street, Waltham, Massachusetts, 02453, USA

    Megan Bogalhas

Authors
  1. Sven Loebrich
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  2. Mingfang Shen
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  3. Erika Cohen
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  4. Gillian Payne
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  5. Ying Chen
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  6. Megan Bogalhas
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  7. Yiwei Zhao
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Correspondence to Sven Loebrich.

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Loebrich, S., Shen, M., Cohen, E. et al. Development and Characterization of a Neutralizing Anti-idiotype Antibody Against Mirvetuximab for Analysis of Clinical Samples. AAPS J 19, 1223–1234 (2017). https://doi.org/10.1208/s12248-017-0098-0

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  • DOI: https://doi.org/10.1208/s12248-017-0098-0

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