Defining the optimal murine models to investigate immune checkpoint blockers and their combination with other immunotherapies

The lack of suitable animal models to study human immune response is an important limitation to the preclinical development of drugs targeting immune cells. In this regard, we have reviewed the strengths and weaknesses of available animal models to study checkpoint blockers. Humanized mice models are the most promising ones, since they facilitate the study of human immune responses against human tumors in a murine organism.The recent success of checkpoint blockers to treat cancer has demonstrated that the immune system is a critical player in the war against cancer. Historically, anticancer therapeutics have been tested in syngeneic mouse models (with a fully murine immune system) or in immunodeficient mice that allow the engraftment of human xenografts. Animal models with functioning human immune systems are critically needed to more accurately recapitulate the complexity of the human tumor microenvironment. Such models are integral to better predict tumor responses to both immunomodulatory agents and directly antineoplastic therapies. In this regard, the development of humanized models is a promising, novel strategy that offers the possibility of testing checkpoint blockers' capacity and their combination with other antitumor drugs. In this review, we discuss the strengths and weaknesses of the available animal models regarding their capacity to evaluate checkpoint blockers and checkpoint blocker-based combination immunotherapy.