Mouse Tumor Models for Advanced Cancer Immunotherapy

Abstract

Recent advances in the development of new methods of cancer immunotherapy require the production of complex cancer animal models that reliably reflect the complexity of the tumor and its microenvironment. Mice are good animals to create tumor models because they are low cost, have a short reproductive cycle, exhibit high tumor growth rates, and can be easily genetically modified. However, the obvious problem of these models is the high failure rate observed in human clinical trials after promising results obtained in mouse models. In order to increase the reliability of the results obtained in mice, the tumor model should reflect the heterogeneity of the tumor, contain components of the tumor microenvironment, in particular immune cells, to which the action of immunotherapeutic drugs are directed. This review discusses the current immunocompetent and immunocompromised mouse models of human tumors that are used to evaluate the effectiveness of immunotherapeutic agents, in particular chimeric antigen receptor (CAR) T-cells and immune checkpoint inhibitors.

Keywords: CAR T-cell therapy; cancer immunotherapy; cancer mouse models; immune checkpoint inhibitors.

Figure 1

Production of mouse tumor models for evaluation of immunotherapy. (A) Syngeneic tumor models are produced by transplanting mouse tumor cell lines into immunocompetent animals in a short period of time. (B) In genetically engineered tumor models, the tumor forms de novo as a result of specific genome modification. (C) In mice treated with carcinogens, the tumor also forms spontaneously de novo. (D) For the production of patient-derived xenograft (PDX) models with human immune system immunocompromised mice can be humanized with peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs), and after that transplanted with a human tumor.