Mouse models have been the workhorses of preclinical immuno-oncology (IO) research, and advances in mouse model development have expanded to applications for nearly all types of solid tumors and hematological malignancies. Preclinical evaluation of experimental immunotherapies has been advanced by syngeneic and humanized mouse models. Syngeneic mice are one of the most established types of models used in cancer research, whereas humanized mice are contemporary mouse model that has been critical to the screening of immunotherapeutic agents. Here we highlight features of syngeneic and humanized mouse models and define which models are most relevant to different phases of preclinical IO research.

Mouse models have been essential to the development of novel immunotherapies that target solid tumors and hematological malignancies. Several types of mouse models exist, and syngeneic mouse models offer several advantages for screening potential drugs and biologics since tumors are derived from the same genetic background as the mouse strain. Syngeneic tumor models are particularly useful for profiling tumor infiltrating lymphocytes (TILs) that are found within the tumor microenvironment (TME) of solid tumors.

Highlighted below is how immune profiling of TILs can be carried out in syngeneic mouse models and how this informs preclinical studies.

A wide range of mouse models are currently available to researchers working on the preclinical development of oncology therapeutics. Syngeneic mouse models, also known as allograft mouse tumor models, are mice engrafted with mouse-derived cancer cell lines. These mice have an intact murine immune system and thus are appealing for proof-of-concept immuno-oncology studies. However, one limitation of traditional syngeneic models is that they are not suitable for human-specific therapies. To overcome this, scientists have developed genetically engineered mice that express human immune targets, such as PD-1, PD-L1, CTLA4 and OX40, in an otherwise immunocompetent model. Tumor cell lines have been developed that also express immune checkpoint molecules, which can have a significant effect on the efficacy of potential immune checkpoint inhibitors being evaluated.