Sökning: onr:"swepub:oai:lup.lub.lu.se:178f5362-5aff-4c9a-9af4-d439c48e2dfd" >
IL-2-mediated hepat...
IL-2-mediated hepatotoxicity : knowledge gap identification based on the irAOP concept
-
- Roser, Luise A. (författare)
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
-
- 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
-
- 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
-
visa fler...
-
- Neuhaus, Vanessa (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
-
- Dehmel, Susann (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
-
- Sommer, Charline (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
-
- Raasch, Martin (författare)
- Dynamic42 GmbH
-
- Flandre, Thierry (författare)
- Novartis Institutes of Biomedical Research, Switzerland
-
- Roesener, Sigrid (författare)
- Merck Healthcare KGaA
-
- Hewitt, Philip (författare)
- Merck Healthcare KGaA
-
- Parnham, Michael J. (författare)
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
-
- Sewald, Katherina (författare)
- Fraunhofer Institute for Toxicology and Experimental Medicine
-
- Schiffmann, Susanne (författare)
- EpiEndo Pharmaceuticals ehf.
-
visa färre...
-
(creator_code:org_t)
- 2024
- 2024
- Engelska.
-
Ingår i: Journal of Immunotoxicology. - 1547-691X. ; 21:1
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
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
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Roser, Luise A.
-
Sakellariou, Chr ...
-
Lindstedt, Malin
-
Neuhaus, Vanessa
-
Dehmel, Susann
-
Sommer, Charline
-
visa fler...
-
Raasch, Martin
-
Flandre, Thierry
-
Roesener, Sigrid
-
Hewitt, Philip
-
Parnham, Michael ...
-
Sewald, Katherin ...
-
Schiffmann, Susa ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Farmakologi och ...
- Artiklar i publikationen
-
Journal of Immun ...
- Av lärosätet
-
Lunds universitet