Related Experiment Video
Updated: Apr 27, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Human cancer growth and therapy in immunodeficient mouse models
Leonard D Shultz1, Neal Goodwin1, Fumihiko Ishikawa2
1The Jackson Laboratory, Bar Harbor, Maine 04609;
Abstract:
Since the discovery of the "nude" mouse more than 40 years ago, investigators have attempted to model human tumor growth in immunodeficient mice. Here, we summarize how the field has advanced over the ensuing years owing to improvements in the murine recipients of human tumors. These improvements include the discovery of the scid mutation and development of targeted mutations in the recombination-activating genes 1 and 2 (Rag1(null), Rag2(null)) that severely cripple the adaptive immune response of the murine host. More recently, mice deficient in adaptive immunity have been crossed with mice bearing targeted mutations designed to weaken the innate immune system, ultimately leading to the development of immunodeficient mice bearing a targeted mutation in the gene encoding the interleukin 2 (IL2) receptor common γ chain (IL2rg(null), also known in humans as cytokine receptor common subunit γ). The IL2rg(null) mutation has been used to develop several immunodeficient strains of mice, including the NOD-scid IL2rg(null) (NSG) strain. Using NSG mice as human xenograft recipients, it is now possible to grow almost all types of primary human tumors in vivo, including most solid tumors and hematological malignancies that maintain characteristics of the primary tumor in the patient. Programs to optimize patient-specific therapy using patient-derived xenograft tumor growth in NSG mice have been established at several institutions, including The Jackson Laboratory. Moreover, NSG mice can be engrafted with functional human immune systems, permitting for the first time the potential to study primary human tumors in vivo in the presence of a human immune system.
Insights
Advances in immunodeficient mice, like NSG strains, now enable modeling of nearly all human tumors. These models facilitate patient-specific therapy development and studying human tumors with functional human immune systems.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- The development of immunodeficient mouse models is crucial for studying human tumor growth in vivo.
- Early models like the "nude" mouse provided foundational capabilities but had limitations.
Purpose of the Study:
- To review the advancements in immunodeficient mouse models for human tumor xenografts.
- To highlight the capabilities of the latest generation of immunodeficient mice, particularly NSG strains.
Main Methods:
- Progressive genetic engineering of mice to impair adaptive and innate immune responses.
- Development of severe combined immunodeficiency (SCID) and recombination-activating gene (Rag) mutations.
- Introduction of interleukin-2 receptor gamma chain (IL2rg) deficiency, leading to strains like NOD-scid IL2rg(null) (NSG).
Main Results:
- NSG mice support the engraftment and growth of nearly all primary human tumor types, including solid tumors and hematological malignancies.
- These xenografts retain characteristics of the patient's original tumor.
- NSG mice can be engrafted with functional human immune systems, enabling in vivo study of human tumors within a human immune context.
Conclusions:
- Modern immunodeficient mouse models, especially NSG mice, are powerful tools for preclinical cancer research.
- These models are instrumental in developing and optimizing patient-specific therapies.
- The ability to study human tumors with a human immune system in vivo opens new avenues for translational research.
