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Table 1 Characteristic features of available pre-clinical murine tumor models

From: Combination immunotherapy: a road map

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
  1. GEMM genetically-engineered mouse model; PDX patient-derived xenograft