Mouse-in-mouse models

ModelExamplesCharacteristicsPossible 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