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 |