Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development
Immunogenicity assessment during early stages of nonclinical biotherapeutic development is not always warranted. It is rarely predictive for clinical studies and evidence for the presence of anti-drug antibodies (ADAs) may be inferred from the pharmacokinetic (PK) profile. However, collecting and ba...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2618575 |
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| _version_ | 1832566859885445120 |
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| author | Montserrat Carrasco-Triguero Helen Davis Yuda Zhu Daniel Coleman Denise Nazzal Paul Vu Surinder Kaur |
| author_facet | Montserrat Carrasco-Triguero Helen Davis Yuda Zhu Daniel Coleman Denise Nazzal Paul Vu Surinder Kaur |
| author_sort | Montserrat Carrasco-Triguero |
| collection | DOAJ |
| description | Immunogenicity assessment during early stages of nonclinical biotherapeutic development is not always warranted. It is rarely predictive for clinical studies and evidence for the presence of anti-drug antibodies (ADAs) may be inferred from the pharmacokinetic (PK) profile. However, collecting and banking samples during the course of the study are prudent for confirmation and a deeper understanding of the impact on PK and safety. Biotherapeutic-specific ADA assays commonly developed can require considerable time and resources. In addition, the ADA assay may not be ready when needed if the study of PK and safety data triggers assay development. During early stages of drug development for antibody-drug conjugates (ADCs), there is the added complication of the potential inclusion of several molecular variants in a study, differing in the linker and/or drug components. To simplify analysis of ADAs at this stage, we developed plug-and-play generic approaches for both the assay format and the data analysis steps. Firstly, the assay format uses generic reagents to detect ADAs. Secondly, we propose a cut point methodology based on animal specific baseline variability instead of a population data approach. This assay showed good sensitivity, drug tolerance, and reproducibility across a variety of antibody-derived biotherapeutics without the need for optimization across molecules. |
| format | Article |
| id | doaj-art-e27dea89915149588d819f489c4a60d3 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-e27dea89915149588d819f489c4a60d32025-02-03T01:03:03ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/26185752618575Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug DevelopmentMontserrat Carrasco-Triguero0Helen Davis1Yuda Zhu2Daniel Coleman3Denise Nazzal4Paul Vu5Surinder Kaur6BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USABioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USABiostatistics (MDBB), Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USABiostatistics (MDBB), Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USABioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USABioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USABioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USAImmunogenicity assessment during early stages of nonclinical biotherapeutic development is not always warranted. It is rarely predictive for clinical studies and evidence for the presence of anti-drug antibodies (ADAs) may be inferred from the pharmacokinetic (PK) profile. However, collecting and banking samples during the course of the study are prudent for confirmation and a deeper understanding of the impact on PK and safety. Biotherapeutic-specific ADA assays commonly developed can require considerable time and resources. In addition, the ADA assay may not be ready when needed if the study of PK and safety data triggers assay development. During early stages of drug development for antibody-drug conjugates (ADCs), there is the added complication of the potential inclusion of several molecular variants in a study, differing in the linker and/or drug components. To simplify analysis of ADAs at this stage, we developed plug-and-play generic approaches for both the assay format and the data analysis steps. Firstly, the assay format uses generic reagents to detect ADAs. Secondly, we propose a cut point methodology based on animal specific baseline variability instead of a population data approach. This assay showed good sensitivity, drug tolerance, and reproducibility across a variety of antibody-derived biotherapeutics without the need for optimization across molecules.http://dx.doi.org/10.1155/2016/2618575 |
| spellingShingle | Montserrat Carrasco-Triguero Helen Davis Yuda Zhu Daniel Coleman Denise Nazzal Paul Vu Surinder Kaur Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development Journal of Immunology Research |
| title | Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development |
| title_full | Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development |
| title_fullStr | Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development |
| title_full_unstemmed | Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development |
| title_short | Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development |
| title_sort | application of a plug and play immunogenicity assay in cynomolgus monkey serum for adcs at early stages of drug development |
| url | http://dx.doi.org/10.1155/2016/2618575 |
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