Journal
NATURE REVIEWS CLINICAL ONCOLOGY
Volume 20, Issue 3, Pages 192-206Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41571-022-00721-2
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Immunotherapy has shown promise in treating various cancers, but there is still much to learn about its mechanisms of action and biomarkers of response. Humanized mice, which are mice engrafted with human tumors and immune components, offer several advantages for immuno-oncology research. This Review discusses the benefits and challenges of humanized mice and highlights the latest advances in their generation for potential clinical translation.
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.
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