Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept
The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2345158 |
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| author | Miriam Alb Kristin Reiche Michael Rade Katherina Sewald Peter Loskill Madalena Cipriano Tengku Ibrahim Maulana Andries D. van der Meer Huub J. Weener Laure-Alix Clerbaux Birgit Fogal Nirav Patel Karissa Adkins Emma Lund Ethan Perkins Christopher Cooper Jan van den Brulle Hannah Morgan Tina Rubic-Schneider Hui Ling Keith DiPetrillo Jonathan Moggs Ulrike Köhl Michael Hudecek |
| author_facet | Miriam Alb Kristin Reiche Michael Rade Katherina Sewald Peter Loskill Madalena Cipriano Tengku Ibrahim Maulana Andries D. van der Meer Huub J. Weener Laure-Alix Clerbaux Birgit Fogal Nirav Patel Karissa Adkins Emma Lund Ethan Perkins Christopher Cooper Jan van den Brulle Hannah Morgan Tina Rubic-Schneider Hui Ling Keith DiPetrillo Jonathan Moggs Ulrike Köhl Michael Hudecek |
| author_sort | Miriam Alb |
| collection | DOAJ |
| description | The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable in vitro and in vivo models recapitulating the complexity of the human immune system. Additionally, using cells derived from human healthy volunteers in such test systems may not adequately reflect the altered state of the patient's immune system thus potentially underestimating the risk of life-threatening conditions, such as cytokine release syndrome (CRS) following CAR T cell therapy. The IMI2/EU project imSAVAR (immune safety avatar: non-clinical mimicking of the immune system effects of immunomodulatory therapies) aims at creating a platform for novel tools and models for enhanced non-clinical prediction of possible adverse events associated with immunomodulatory therapies. This platform shall in the future guide early non-clinical safety assessment of novel immune therapeutics thereby also reducing the costs of their development. Therefore, we review current opportunities and challenges associated with non-clinical in vitro and in vivo models for the safety assessment of CAR T cell therapy ranging from organ-on-chip models up to advanced biomarker screening. |
| format | Article |
| id | doaj-art-a47eb06e31b042a382f9b941094ae3ec |
| institution | DOAJ |
| issn | 1547-691X 1547-6901 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj-art-a47eb06e31b042a382f9b941094ae3ec2025-08-20T02:48:43ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012024-12-0121sup1S13S2810.1080/1547691X.2024.2345158Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway conceptMiriam Alb0Kristin Reiche1Michael Rade2Katherina Sewald3Peter Loskill4Madalena Cipriano5Tengku Ibrahim Maulana6Andries D. van der Meer7Huub J. Weener8Laure-Alix Clerbaux9Birgit Fogal10Nirav Patel11Karissa Adkins12Emma Lund13Ethan Perkins14Christopher Cooper15Jan van den Brulle16Hannah Morgan17Tina Rubic-Schneider18Hui Ling19Keith DiPetrillo20Jonathan Moggs21Ulrike Köhl22Michael Hudecek23Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, Würzburg, GermanyFraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, GermanyFraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, GermanyFraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM, Hannover, GermanyInstitute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, GermanyApplied Stem Cell Technologies, University of Twente, Enschede, the NetherlandsApplied Stem Cell Technologies, University of Twente, Enschede, the NetherlandsEuropean Commission, Joint Research Centre (JRC), Ispra, ItalyDepartment on Nonclinical Drug Safety, Boehringer Ingelheim Pharmaceutical, Inc, Ridgefield, CT, USAPreclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Cambridge, MA, USAPreclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Cambridge, MA, USALabcorp Drug Development Inc, Derbyshire, UKLabcorp Drug Development Inc, Derbyshire, UKLabcorp Drug Development Inc, Derbyshire, UKT-CURX GmbH, Würzburg, GermanyNovartis Biomedical Research, Novartis Campus, Basel, SwitzerlandNovartis Biomedical Research, Novartis Campus, Basel, SwitzerlandNovartis Biomedical Research, Cambridge, MA, USANovartis Biomedical Research, Cambridge, MA, USANovartis Biomedical Research, Novartis Campus, Basel, SwitzerlandFraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, GermanyMedizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, Würzburg, GermanyThe success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable in vitro and in vivo models recapitulating the complexity of the human immune system. Additionally, using cells derived from human healthy volunteers in such test systems may not adequately reflect the altered state of the patient's immune system thus potentially underestimating the risk of life-threatening conditions, such as cytokine release syndrome (CRS) following CAR T cell therapy. The IMI2/EU project imSAVAR (immune safety avatar: non-clinical mimicking of the immune system effects of immunomodulatory therapies) aims at creating a platform for novel tools and models for enhanced non-clinical prediction of possible adverse events associated with immunomodulatory therapies. This platform shall in the future guide early non-clinical safety assessment of novel immune therapeutics thereby also reducing the costs of their development. Therefore, we review current opportunities and challenges associated with non-clinical in vitro and in vivo models for the safety assessment of CAR T cell therapy ranging from organ-on-chip models up to advanced biomarker screening.https://www.tandfonline.com/doi/10.1080/1547691X.2024.2345158CAR T cellscytokine release syndromenon-clinical safety assessmentimmune-related adverse outcome pathwayorgan-on-a-chipbiomarkers |
| spellingShingle | Miriam Alb Kristin Reiche Michael Rade Katherina Sewald Peter Loskill Madalena Cipriano Tengku Ibrahim Maulana Andries D. van der Meer Huub J. Weener Laure-Alix Clerbaux Birgit Fogal Nirav Patel Karissa Adkins Emma Lund Ethan Perkins Christopher Cooper Jan van den Brulle Hannah Morgan Tina Rubic-Schneider Hui Ling Keith DiPetrillo Jonathan Moggs Ulrike Köhl Michael Hudecek Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept Journal of Immunotoxicology CAR T cells cytokine release syndrome non-clinical safety assessment immune-related adverse outcome pathway organ-on-a-chip biomarkers |
| title | Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept |
| title_full | Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept |
| title_fullStr | Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept |
| title_full_unstemmed | Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept |
| title_short | Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept |
| title_sort | novel strategies to assess cytokine release mediated by chimeric antigen receptor t cells based on the adverse outcome pathway concept |
| topic | CAR T cells cytokine release syndrome non-clinical safety assessment immune-related adverse outcome pathway organ-on-a-chip biomarkers |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2345158 |
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