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Table 1 Mouse-in-mouse models

From: Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer

Model Examples Characteristics Possible Improvements
Genetically engineered (GEMMs) • Transgenic
• Knock-in/out
• Long latency
• Incomplete penetrance
• Few somatic mutations
• Physiological mitotic rate and tumor microenvironment
• Low rate of metastasis
• Difficult to induce effective immune responses
• High bar for therapies being tested and potentially good model to mimic immunologically incompetent tumors
• Increasing antigenicity
Mutator alleles
Chemical carcinogenesis
Model antigens
• Enhanced immune backgrounds
Chemically induced • 3′methylcholanthrene (MCA) • Fully penetrant
• Variable latency
• Unclear histological cancer type
• High number of somatic mutations
• Can be very immunogenic
• Often used as syngeneic grafts
 
Syngeneic • Engraftment of mouse cancer cell lines
B16, MC38, CT26, RMA, YUMM, etc.
• Easy, inexpensive, and fast to use
• Typically subcutaneous injection of cells
• Tumor can grow very quickly
• Variable immunogenicity
• Variable response to immunotherapy
• Hard to compare across models
• Drive genes are frequently unknown
• Contribution of endogenous retrovirus is not known
• Mutation burden is frequently high
• Use multiple lines driven by human-relevant genetic changes
• Series of similar lines with variable mutational burden
• Ability to evaluate antigen-specific responses
• Advanced imaging available to follow immune responses sequentially
• Evaluate anti-tumor response at metastatic sites
• Make lines from inbred cells using CRISPR