Humanized mouse models for immuno-oncology research

人性化鼠标 医学 免疫疗法 免疫系统 临床前研究 临床试验 药物开发 转化研究 免疫学 癌症研究 计算生物学 生物信息学 药品 生物 内科学 药理学 病理 医学物理学
作者
Jane Chuprin,Hannah Buettner,Mina O. Seedhom,Dale L. Greiner,James Keck,Fumihiko Ishikawa,Leonard D. Shultz,Michael A. Brehm
出处
期刊:Nature Reviews Clinical Oncology [Nature Portfolio]
卷期号:20 (3): 192-206 被引量:216
标识
DOI:10.1038/s41571-022-00721-2
摘要

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. Preclinical models that faithfully recapitulate interactions between the human immune system and tumours are necessary to evaluate human-specific immunotherapies in vivo; however, their number is currently limited. The authors of this Review discuss the currently available humanized mouse models, which are immunodeficient mice co-engrafted with human tumours and immune components, with a focus on their applicability in translational research.
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