Characteristic features of available pre-clinical murine tumor models
| Model | Advantages | Disadvantages |
|---|---|---|
| Transplantable tumor • syngeneic murine • xenografts from human cancer cells lines • patient-derived xenografts (PDX) | • Tumors usually grow quickly• Reliable and reproducible• Can use different tumor cell lines• Gene expression easily manipulated in cell lines | • Rapid tumor growth may not allow time for physiologic immune system interactions• Does not mimic natural tumor formation• Tumor microenvironment is not relevant• Local injections can result in inflammation altering normal host response• Genetic engineering may create xenoantigens |
| Orthotopic tumor | • Allows normal tumor microenvironment to develop• Maintains many of the advantages of transplantable tumors | • Often grow quickly and do not allow interactions with immune system• May be challenging to get tumor injected or to establish in native tissue or organ |
| Spontaneous tumor • Carcinogen-induced • Genetically-mediated (GEMM) | • Tumors arise in situ• Tumors develop with host microenvironment• Tumors may have transgenic expression of oncogenes or inactivation of tumor suppressor genes• Tumors may exhibit more physiologic tumor growth kinetics and response to treatment• Assessment of toxicity is more relevant to humans | • Tumors may take more time to develop• Heterogeneity may arise and require more animals to determine therapeutic responses• Tumor induction may require carcinogens or genetic manipulations that alter the natural course of tumor development• Other cells may be affected• Tumor monitoring may be difficult |
| Immunodeficient mice | • Allows study of specific immune components• Can accept range of allogeneic and xenogeneic tumor cells• Can be used to introduce specific immune effector cells through adoptive transfer | • May be prone to infection and limited lifespan• May not be able to determine impact on intact immune system• Leakiness can result in unanticipated immune activity• May be sensitive to radiation and other treatments |
| Humanized mice | • Allow more rapid study of human tumors and human immune system• May more accurately replicate human tumor/immune system interactions | • Engraftment may be low• Murine immune system may interfere with human elements• Access to human samples can be challenging• Expensive |
GEMM genetically-engineered mouse model; PDX patient-derived xenograft