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

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Immunotoxicology, Vol 21, Iss sup1, Pp S13-S28 (2024)
Druh dokumentu: article
ISSN: 1547691X
1547-6901
1547-691X
DOI: 10.1080/1547691X.2024.2345158
Popis: 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: Directory of Open Access Journals
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