Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept.

Autor: Alb M; Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, Würzburg, Germany., Reiche K; Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany., Rade M; Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany., Sewald K; Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM, Hannover, Germany., Loskill P; Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.; 3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen.; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Cipriano M; Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.; 3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen., Maulana TI; Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.; 3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen., van der Meer AD; Applied Stem Cell Technologies, University of Twente, Enschede, the Netherlands., Weener HJ; Applied Stem Cell Technologies, University of Twente, Enschede, the Netherlands., Clerbaux LA; European Commission, Joint Research Centre (JRC), Ispra, Italy., Fogal B; Department on Nonclinical Drug Safety, Boehringer Ingelheim Pharmaceutical, Inc, Ridgefield, CT, USA., Patel N; Preclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Cambridge, MA, USA., Adkins K; Preclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Cambridge, MA, USA., Lund E; Labcorp Drug Development Inc, Derbyshire, UK., Perkins E; Labcorp Drug Development Inc, Derbyshire, UK., Cooper C; Labcorp Drug Development Inc, Derbyshire, UK., van den Brulle J; T-CURX GmbH, Würzburg, Germany., Morgan H; Novartis Biomedical Research, Novartis Campus, Basel, Switzerland., Rubic-Schneider T; Novartis Biomedical Research, Novartis Campus, Basel, Switzerland., Ling H; Novartis Biomedical Research, Cambridge, MA, USA., DiPetrillo K; Novartis Biomedical Research, Cambridge, MA, USA., Moggs J; Novartis Biomedical Research, Novartis Campus, Basel, Switzerland., Köhl U; Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany., Hudecek M; Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, Würzburg, Germany.; Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany.
Jazyk: angličtina
Zdroj: Journal of immunotoxicology [J Immunotoxicol] 2024 Oct; Vol. 21 (sup1), pp. S13-S28. Date of Electronic Publication: 2024 Dec 10.
DOI: 10.1080/1547691X.2024.2345158
Abstrakt: 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.
Databáze: MEDLINE