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Updated: Jul 19, 2025
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Humanized Mouse Models for Immuno-oncology Drug Discovery
Rajendra Kumari1, Gerold Feuer1, Ludovic Bourré1
1Crown Bioscience Inc., San Diego, California, USA.
Abstract:
Breakthroughs in cancer treatment with immunotherapeutics have provided long-term patient benefits for many different types of cancer. However, complete response is not achieved in many patients and tumor types, and the mechanisms underlying this lack of response are poorly understood. Despite this, numerous new targets, therapeutics, and drug combinations are being developed and tested in clinical trials. Preclinical models that recapitulate the complex human tumor microenvironment and the interplay between tumor and immune cells within the cancer-immunity cycle are needed to improve our understanding and screen new therapeutics for efficacy and safety/toxicity. Humanized mice, encompassing human tumors and human immune cells engrafted on immunodeficient mice, have been widely used for many years in immuno-oncology, with developments to improve both the humanization and the translational value central to the next generation of models. In this overview, we discuss recent advances in humanized models relevant to immuno-oncology drug discovery, the advantages and limitations of such models, the application of humanized models for efficacy and safety assessments of immunotherapeutics, and the potential opportunities. © 2023 Crown Bioscience. Current Protocols published by Wiley Periodicals LLC.
Insights
Humanized mice models improve understanding of cancer-immunity cycles and aid in developing novel immunotherapeutics. These advanced preclinical models are crucial for assessing treatment efficacy and safety in immuno-oncology drug discovery.
Area of Science:
- Immuno-oncology
- Translational research
- Preclinical drug development
Background:
- Immunotherapeutics offer long-term cancer patient benefits, but response rates vary, and resistance mechanisms remain unclear.
- Effective preclinical models are essential for understanding the tumor microenvironment and screening novel cancer treatments.
- Humanized mice, incorporating human tumors and immune cells, are valuable tools in immuno-oncology research.
Purpose of the Study:
- To review recent advancements in humanized mouse models for immuno-oncology drug discovery.
- To discuss the benefits and drawbacks of these models in cancer research.
- To explore their application in evaluating immunotherapeutic efficacy and safety.
Main Methods:
- Overview of humanized mouse models, including human tumor and immune cell engraftment.
- Discussion of model improvements focusing on humanization and translational relevance.
- Analysis of applications in efficacy and safety/toxicity assessments of immunotherapeutics.
Main Results:
- Humanized models offer a more comprehensive recapitulation of the human tumor microenvironment.
- These models facilitate the study of complex interactions within the cancer-immunity cycle.
- Recent developments enhance the translational value of humanized mice for drug discovery.
Conclusions:
- Humanized mouse models are pivotal for advancing immuno-oncology drug discovery.
- Continued development of these models is key to overcoming challenges in cancer treatment.
- They provide critical insights for the efficacy and safety evaluation of novel immunotherapeutics.
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