用于免疫肿瘤学研究的人类化小鼠模型。
Humanized mouse models for immuno-oncology research.
发表日期:2023 Mar
作者:
Jane Chuprin, Hannah Buettner, Mina O Seedhom, Dale L Greiner, James G Keck, Fumihiko Ishikawa, Leonard D Shultz, Michael A Brehm
来源:
Nature Reviews Clinical Oncology
摘要:
免疫疗法已成为许多恶性肿瘤的有希望的治疗范例,正在改变药物开发的格局。虽然免疫疗法剂显示了临床疗效,但它们与不同的临床反应相关,并且我们对它们的作用机制和特定反应生物标志物的理解仍有很大的差距。目前,可以真实复现人类免疫系统与肿瘤相互作用,并且能在活体内评估人类特异性免疫疗法的临床前模型数量有限。人源小鼠是一种免疫缺陷小鼠,与人类肿瘤和免疫组分同时植入,为免疫肿瘤学研究提供了几个优势。在本综述中,我们讨论了目前可用的人源小鼠的优势和挑战,包括植入人类肿瘤和免疫组分之间的特定相互作用,以及这些小鼠中人类先天免疫群体的发展和生存状况,以及研究植入与患者匹配的肿瘤和免疫细胞的小鼠的方法。我们强调了人源小鼠模型制备的最新进展,旨在为其在潜在临床转化的免疫肿瘤学研究中的应用提供指导。 ©2023 Springer Nature Limited。
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.© 2023. Springer Nature Limited.