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Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice
Beatrice Campilan1, Christian Schroeder1, Emilija Sagaityte1
1Department of Neurosurgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States.
Abstract:
Animal models have been commonly used in immunotherapy research to study the cell response to external agents and to assess the effectiveness and safety of new therapies. Over the past few decades, immunocompromised (also called immunodeficient) mice allowed researchers to grow human tumor cells without the impact of the host's immune system. However, while this model is very valuable to understand the tumor biology and to understand the underlying mechanism of immunotherapy, the results may not always directly translate to humans. The tumor microenvironment has significant implications for tumor engraftment, growth, invasion, etc., and the immune system plays a critical role in shaping the tumor microenvironment. Human immunocompetent mice, also named humanized mice, are engineered mice that possess functional human immune cells. This in vivo model can be used to effectively study the effect of the human immune system to a human implanted tumor. Moreover, this can effectively mimic the response to treatment. This section is an overview of the current understanding of the different humanized mice that could be utilized to mimic the tumor microenvironment in chordoma.
Insights
Humanized mice, engineered with functional human immune cells, offer a more accurate model for studying immunotherapy and the tumor microenvironment in chordoma research compared to traditional immunocompromised models.
Area of Science:
- Immunology
- Oncology
- Translational Research
Background:
- Traditional immunocompromised mouse models are valuable for tumor biology and immunotherapy mechanisms but may not fully translate to human responses.
- The tumor microenvironment, significantly shaped by the immune system, is crucial for tumor progression and treatment response.
- Existing models often lack the human immune component necessary for accurate immunotherapy assessment.
Purpose of the Study:
- To provide an overview of humanized mice as advanced models for studying the tumor microenvironment in chordoma.
- To highlight the advantages of humanized mice over traditional models for immunotherapy research.
- To discuss the potential of humanized mice in mimicking human immune responses to chordoma.
Main Methods:
- Review of current literature on humanized mouse models.
- Analysis of the immunological components within humanized mice.
- Comparison of humanized mice with immunocompromised models for tumor microenvironment studies.
Main Results:
- Humanized mice possess functional human immune cells, enabling a more relevant study of human tumor-immune interactions.
- These models can effectively mimic the human immune system's response to implanted human tumors.
- Humanized mice provide a superior platform for assessing immunotherapy effectiveness and safety in a human-like tumor microenvironment.
Conclusions:
- Humanized mice represent a significant advancement in preclinical cancer research, particularly for immunotherapy.
- Their ability to replicate the human immune system and tumor microenvironment makes them invaluable for chordoma research.
- Further utilization of humanized mice is recommended for developing more effective chordoma therapies.
