Humanized Mouse as a Tool to Predict Immunotoxicity of Human Biologics
Name
fimmu-11-553362.pdf
Description
Published version
Size
1.91 MB
Format
Unknown
Checksum (MD5)
d943eb9ff548a466dbe5afbc9e921cb7
Author(s)
Yong, Kylie Su Mei
Her, Zhisheng
Tan, Sue Yee
Tan, Wilson Wei Sheng
Liu, Min
Lai, Fritz
Heng, Shi Min
Fan, Yong
Chang, Kenneth Tou En
Wang, Cheng-I
Date Issued
October 2020
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Version
Final published version
Abstract
© Copyright © 2020 Yong, Her, Tan, Tan, Liu, Lai, Heng, Fan, Chang, Wang, Chan, Chen and Chen. 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.
MIT Department
Singapore-MIT Alliance in Research and Technology (SMART)
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3389/fimmu.2020.553362
