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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