Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates
Unwanted immunogenicity of therapeutic proteins arises through the combination of many factors, with the route of administration considered a significant contributor. Contrary to historic data on vaccine delivery, analysis of various therapeutic protein products indicates that the subcutaneous route...
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2025.2537408 |
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| author | Victoria Koch Martin Lechmann Katharine Bray-French Matthias Füth Elisabeth Husar Niels Janssen Anneliese Schneider Kay Stubenrauch Timothy Hickling Sven Kronenberg |
| author_facet | Victoria Koch Martin Lechmann Katharine Bray-French Matthias Füth Elisabeth Husar Niels Janssen Anneliese Schneider Kay Stubenrauch Timothy Hickling Sven Kronenberg |
| author_sort | Victoria Koch |
| collection | DOAJ |
| description | Unwanted immunogenicity of therapeutic proteins arises through the combination of many factors, with the route of administration considered a significant contributor. Contrary to historic data on vaccine delivery, analysis of various therapeutic protein products indicates that the subcutaneous route is not a systematic risk. However, individual product assessments may identify factors specific to the circumstance of their use. Preclinical in vivo studies may add additional information to the comparative immunogenicity risk assessment of intravenous versus subcutaneous administrations. Moreover, immunogenicity risk assessment of new biotherapeutic modalities, such as bispecific antibodies and antibody-linked cytokines, may benefit from a full analysis of risk factors, including preclinical in vivo data. The study here provides immunogenicity analysis of an IgG, two CD3 bispecific antibodies, and two Fc-linked immunocytokines administered intravenously and subcutaneously, aiming to highlight similarities and differences between these administration routes. The current results suggest that the development of anti-drug antibodies does not solely depend on the route of administration but is influenced by multiple risk factors, which should be addressed on a case-by-case basis. This paper reflects on the challenges of interpreting the data and propose standards for improving sample and data collection to aid future analysis. |
| format | Article |
| id | doaj-art-3b3d366e4cbc431a8fb416d68d9e43ac |
| institution | Kabale University |
| issn | 1547-691X 1547-6901 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj-art-3b3d366e4cbc431a8fb416d68d9e43ac2025-08-20T03:40:28ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012025-12-0122110.1080/1547691X.2025.2537408Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primatesVictoria Koch0Martin Lechmann1Katharine Bray-French2Matthias Füth3Elisabeth Husar4Niels Janssen5Anneliese Schneider6Kay Stubenrauch7Timothy Hickling8Sven Kronenberg9Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Munich, GermanyRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Zurich, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Munich, GermanyRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, SwitzerlandUnwanted immunogenicity of therapeutic proteins arises through the combination of many factors, with the route of administration considered a significant contributor. Contrary to historic data on vaccine delivery, analysis of various therapeutic protein products indicates that the subcutaneous route is not a systematic risk. However, individual product assessments may identify factors specific to the circumstance of their use. Preclinical in vivo studies may add additional information to the comparative immunogenicity risk assessment of intravenous versus subcutaneous administrations. Moreover, immunogenicity risk assessment of new biotherapeutic modalities, such as bispecific antibodies and antibody-linked cytokines, may benefit from a full analysis of risk factors, including preclinical in vivo data. The study here provides immunogenicity analysis of an IgG, two CD3 bispecific antibodies, and two Fc-linked immunocytokines administered intravenously and subcutaneously, aiming to highlight similarities and differences between these administration routes. The current results suggest that the development of anti-drug antibodies does not solely depend on the route of administration but is influenced by multiple risk factors, which should be addressed on a case-by-case basis. This paper reflects on the challenges of interpreting the data and propose standards for improving sample and data collection to aid future analysis.https://www.tandfonline.com/doi/10.1080/1547691X.2025.2537408Immunogenicityadministration routesubcutaneousintravenousnon-human primate |
| spellingShingle | Victoria Koch Martin Lechmann Katharine Bray-French Matthias Füth Elisabeth Husar Niels Janssen Anneliese Schneider Kay Stubenrauch Timothy Hickling Sven Kronenberg Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates Journal of Immunotoxicology Immunogenicity administration route subcutaneous intravenous non-human primate |
| title | Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates |
| title_full | Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates |
| title_fullStr | Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates |
| title_full_unstemmed | Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates |
| title_short | Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates |
| title_sort | comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non human primates |
| topic | Immunogenicity administration route subcutaneous intravenous non-human primate |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2025.2537408 |
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