Table 1 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 |