Related Experiment Video
Updated: Nov 30, 2025
Production of Humanized Mouse via Thymic Renal Capsule Grafting, CD34+ Cells Injection, and Cytokine Delivery
Published on: September 27, 2021
Humanized Mouse as a Tool to Predict Immunotoxicity of Human Biologics
Kylie Su Mei Yong1, Zhisheng Her1, Sue Yee Tan1
1Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Abstract:
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.
Insights
Humanized mice models effectively predict biologic drug immunotoxicity by recapitulating human immune responses observed in clinical trials. This preclinical model enhances biologic safety assessments, reducing risks for research participants.
Area of Science:
- Immunology
- Pharmacology
- Biotechnology
Background:
- Non-human animal models inadequately predict human immune responses to biologics.
- Lack of predictive models leads to adverse effects in clinical trials.
- Understanding in vivo human immune interactions is crucial for biologic development.
Purpose of the Study:
- To evaluate humanized mice as a model for assessing biologic immunotoxicity.
- To compare immunotoxic effects of IL-2 and OKT3 in humanized mice with clinical outcomes.
Main Methods:
- Utilized humanized mice (reconstituted with human fetal cells).
- Administered known immunotoxic biologics (Proleukin®/IL-2, OKT3).
- Compared observed in vivo responses to published clinical data.
Main Results:
- Humanized mice recapitulated in vivo pathological changes.
- Observed human-specific immune responses, including elevated cytokines and modulated immune cell subsets.
- Demonstrated high similarity between humanized mouse model and clinical study outcomes.
Conclusions:
- Humanized mice accurately model in vivo immunotoxicity of biologics.
- This preclinical model can predict human immune responses to novel biologics.
- The model offers a safer alternative for assessing biologic immunotoxicity before human trials.
