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Tytuł pozycji:

Humanized Mouse as a Tool to Predict Immunotoxicity of Human Biologics.

Tytuł :
Humanized Mouse as a Tool to Predict Immunotoxicity of Human Biologics.
Autorzy :
Yong KSM; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Her Z; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Tan SY; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Tan WWS; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Liu M; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Lai F; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Heng SM; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Fan Y; Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Chang KTE; Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore.; Department of Pathology, Duke-NUS Graduate Medical School, Singapore, Singapore.
Wang CI; Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Chan JKY; Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore.; Experimental Fetal Medicine Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Chen J; Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore, Singapore.; The Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States.
Chen Q; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.; Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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Źródło :
Frontiers in immunology [Front Immunol] 2020 Oct 15; Vol. 11, pp. 553362. Date of Electronic Publication: 2020 Oct 15 (Print Publication: 2020).
Typ publikacji :
Journal Article; Research Support, Non-U.S. Gov't
Język :
English
Imprint Name(s) :
Original Publication: [Lausanne : Frontiers Research Foundation]
MeSH Terms :
Models, Immunological*
Interleukin-2/*analogs & derivatives
Animals ; Drug Evaluation ; Fetus ; Humans ; Interleukin-2/adverse effects ; Interleukin-2/immunology ; Interleukin-2/pharmacology ; Mice ; Recombinant Proteins/adverse effects ; Recombinant Proteins/immunology ; Recombinant Proteins/pharmacology
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Contributed Indexing :
Keywords: biologic testing*; cytokine storm*; humanized mice*; immunotoxicity*; inflammation*
Substance Nomenclature :
0 (Interleukin-2)
0 (Recombinant Proteins)
M89N0Q7EQR (aldesleukin)
Entry Date(s) :
Date Created: 20201116 Date Completed: 20210430 Latest Revision: 20210430
Update Code :
20210506
PubMed Central ID :
PMC7604536
DOI :
10.3389/fimmu.2020.553362
PMID :
33193321
Czasopismo naukowe
Advancements in science enable researchers to constantly innovate and create novel biologics. However, the use of non-human animal models during the development of biologics impedes identification of precise in vivo interactions between the human immune system and treatments. Due to lack of this understanding, adverse effects are frequently observed in healthy volunteers and patients exposed to potential biologics during clinical trials. In this study, we evaluated and compared the effects of known immunotoxic biologics, Proleukin ® /IL-2 and OKT3 in humanized mice (reconstituted with human fetal cells) to published clinical outcomes. We demonstrated that humanized mice were able to recapitulate in vivo pathological changes and human-specific immune responses, such as elevated cytokine levels and modulated lymphocytes and myeloid subsets. Given the high similarities of immunological side effects observed between humanized mice and clinical studies, this model could be used to assess immunotoxicity of biologics at a pre-clinical stage, without placing research participants and/or patients at risk.
(Copyright © 2020 Yong, Her, Tan, Tan, Liu, Lai, Heng, Fan, Chang, Wang, Chan, Chen and Chen.)

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