Mouse Models for Cancer Immunotherapy Research

Abstract

Immunotherapy has revolutionized cancer therapy, largely attributed to the success of immune-checkpoint blockade. However, there are subsets of patients across multiple cancers who have not shown robust responses to these agents. A major impediment to progress in the field is the availability of faithful mouse models that recapitulate the complexity of human malignancy and immune contexture within the tumor microenvironment. These models are urgently needed across all malignancies to interrogate and predict antitumor immune responses and therapeutic efficacy in clinical trials. Herein, we seek to review pros and cons of different cancer mouse models, and how they can be used as platforms to predict efficacy and resistance to cancer immunotherapies.Significance: Although immunotherapy has shown substantial benefit in the treatment of a variety of malignancies, a key hurdle toward the advancement of these therapies is the availability of immunocompetent preclinical mouse models that recapitulate human disease. Here, we review the evolution of preclinical mouse models and their utility as coclinical platforms for mechanistic interrogation of cancer immunotherapies. Cancer Discov; 8(11); 1358-65. ©2018 AACR.

Figure 1.

Preclinical murine models for evaluation of immuno-oncology agents. A, Syngeneic tumor models utilize murine tumor cell lines that are grown and expanded in vitro and then injected into immunocompetent hosts (commonly either subcutaneously or orthotopically). B, Genetically engineered mouse models incorporate tissue-specific expression of oncogenes or tissue-specific deletion of tumor suppressors, which drives autochthonous tumor cell growth. C, Patient-derived xenografts involve collecting tumor tissue from patients and then injecting into immunodeficient murine hosts and further propagation in vivo. Tumor cells can be injected alone or can be injected along with immune reconstitution using autologous immune cells (from peripheral blood, bone marrow, or selected progenitor populations).