Humanized mouse models for immuno-oncology research.
Humanized mouse models for immuno-oncology research. Nat Rev Clin Oncol. 2023;20(3):192-206.
JMG, JCA, Animals, Mice, Humans, Neoplasms, Disease Models, Animal, Immunotherapy, Biomarkers, Immune System
Nat Rev Clin Oncol. 2023;20(3):192-206.
The work of the authors is supported in part by grants from the US National Institutes of Health (CA034196 (to L.D.S.), AI132963 (to L.D.S. and M.A.B.), OD026440 (to D.L.G., L.D.S. and M.A.B.)) and funding from the Japan Society for the Promotion of Science (to F.I.).
Immunotherapy has emerged as a promising treatment paradigm for many malignancies and is transforming the drug development landscape. Although immunotherapeutic agents have demonstrated clinical efficacy, they are associated with variable clinical responses, and substantial gaps remain in our understanding of their mechanisms of action and specific biomarkers of response. Currently, the number of preclinical models that faithfully recapitulate interactions between the human immune system and tumours and enable evaluation of human-specific immunotherapies in vivo is limited. Humanized mice, a term that refers to immunodeficient mice co-engrafted with human tumours and immune components, provide several advantages for immuno-oncology research. In this Review, we discuss the benefits and challenges of the currently available humanized mice, including specific interactions between engrafted human tumours and immune components, the development and survival of human innate immune populations in these mice, and approaches to study mice engrafted with matched patient tumours and immune cells. We highlight the latest advances in the generation of humanized mouse models, with the aim of providing a guide for their application to immuno-oncology studies with potential for clinical translation.