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Successful Development of Nonclinical Anti-Drug Antibody Assays to Support Zinpentraxin Alfa Reproductive Toxicology Studies.
Arjomandi, Audrey; Siradze, Ketevan; Cheu, Melissa; Davancaze, Teresa; Yadav, Rajbharan; Rao, Gautham K; Wong, Lisa; Fischer, Saloumeh K.
Afiliación
  • Arjomandi A; Department of BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Arjomandi.audrey@gene.com.
  • Siradze K; Department of BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
  • Cheu M; Department of BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
  • Davancaze T; Department of BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
  • Yadav R; Department of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, CA, 94080, USA.
  • Rao GK; Department of Safety Assessment, Genentech, Inc., South San Francisco, CA, 94080, USA.
  • Wong L; Department of Safety Assessment, Genentech, Inc., South San Francisco, CA, 94080, USA.
  • Fischer SK; Department of BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
AAPS J ; 26(1): 16, 2024 01 24.
Article en En | MEDLINE | ID: mdl-38267613
ABSTRACT
Immunogenicity assessment is an essential part of biotherapeutic drug development. While the immune response in animals is not always representative of the human immune response, immunogenicity data obtained in animal models is still informative for the evaluation of drug exposure and safety. The most common assay format used for the detection of anti-drug antibodies (ADAs) in preclinical and clinical studies is the bridging format. The advantage of this method is that it can detect all antibody isotypes generated against the therapeutic. However, the method development can be time-consuming and labor-intensive, due to the need for labeling of the drug which is used both as capture and detection. Various generic ADA assays have been successfully implemented to overcome these disadvantages and to enable faster assay development timelines to support nonclinical toxicology studies. Here, we describe the challenges in the development of an assay to detect antibodies to zinpentraxin alfa, a recombinant human pentraxin-2, in rabbit and rat toxicology studies. Our initial efforts to develop a bridging assay failed, prompting us to develop a method adapted from generic assay formats to detect anti-zinpentraxin alfa antibodies in the serum of different species with minimal optimization. However, while the general assay format remained similar, assay reagents were adapted between the different species, resulting in the development of two distinct assays for the detection of ADAs in rat and rabbit. Here, we share the final development/validation data and the immunogenicity study results. Our work highlights the need for the evaluation of alternate assay formats when evaluating novel drug modalities.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bioensayo / Anticuerpos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: AAPS J Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bioensayo / Anticuerpos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: AAPS J Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos