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IL-2-mediated hepat...
IL-2-mediated hepatotoxicity : knowledge gap identification based on the irAOP concept
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- Roser, Luise A. (författare)
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
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- Sakellariou, Christina (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Lindstedt, Malin (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Neuhaus, Vanessa (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
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- Dehmel, Susann (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
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- Sommer, Charline (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
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- Raasch, Martin (författare)
- Dynamic42 GmbH
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- Flandre, Thierry (författare)
- Novartis Institutes of Biomedical Research, Switzerland
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- Roesener, Sigrid (författare)
- Merck Healthcare KGaA
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- Hewitt, Philip (författare)
- Merck Healthcare KGaA
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- Parnham, Michael J. (författare)
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
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- Sewald, Katherina (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
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- Schiffmann, Susanne (författare)
- EpiEndo Pharmaceuticals ehf.
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: Journal of Immunotoxicology. - 1547-691X. ; 21:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Drug-induced hepatotoxicity constitutes a major reason for non-approval and post-marketing withdrawal of pharmaceuticals. In many cases, preclinical models lack predictive capacity for hepatic damage in humans. A vital concern is the integration of immune system effects in preclinical safety assessment. The immune-related Adverse Outcome Pathway (irAOP) approach, which is applied within the Immune Safety Avatar (imSAVAR) consortium, presents a novel method to understand and predict immune-mediated adverse events elicited by pharmaceuticals and thus targets this issue. It aims to dissect the molecular mechanisms involved and identify key players in drug-induced side effects. As irAOPs are still in their infancy, there is a need for a model irAOP to validate the suitability of this tool. For this purpose, we developed a hepatotoxicity-based model irAOP for recombinant human IL-2 (aldesleukin). Besides producing durable therapeutic responses against renal cell carcinoma and metastatic melanoma, the boosted immune activation upon IL-2 treatment elicits liver damage. The availability of extensive data regarding IL-2 allows both the generation of a comprehensive putative irAOP and to validate the predictability of the irAOP with clinical data. Moreover, IL-2, as one of the first cancer immunotherapeutics on the market, is a blueprint for various biological and novel treatment regimens that are under investigation today. This review provides a guideline for further irAOP-directed research in immune-mediated hepatotoxicity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- adverse event
- Adverse outcome pathway
- drug-induced liver injury
- hepatotoxicity
- immune safety
- immunotherapy
- interleukin-2
- preclinical model
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- Av författaren/redakt...
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Roser, Luise A.
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Sakellariou, Chr ...
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Lindstedt, Malin
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Neuhaus, Vanessa
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Dehmel, Susann
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Sommer, Charline
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visa fler...
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Raasch, Martin
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Flandre, Thierry
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Roesener, Sigrid
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Hewitt, Philip
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Parnham, Michael ...
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Sewald, Katherin ...
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Schiffmann, Susa ...
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visa färre...
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Lunds universitet