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人源化小鼠作为癌症免疫治疗研究的重要临床前模型。

Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research.

作者信息

Cogels Morgane M, Rouas Redouane, Ghanem Ghanem E, Martinive Philippe, Awada Ahmad, Van Gestel Dirk, Krayem Mohammad

机构信息

Department of Radiation Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Laboratory of Clinical and Experimental Oncology (LOCE), Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

出版信息

Front Oncol. 2021 Nov 18;11:784947. doi: 10.3389/fonc.2021.784947. eCollection 2021.

Abstract

Immunotherapy with checkpoint inhibitors opened new horizons in cancer treatment. Clinical trials for novel immunotherapies or unexplored combination regimens either need years of development or are simply impossible to perform like is the case in cancer patients with limited life expectancy. Thus, the need for preclinical models that rapidly and safely allow for a better understanding of underlying mechanisms, drug kinetics and toxicity leading to the selection of the best regimen to be translated into the clinic, is of high importance. Humanized mice that can bear both human immune system and human tumors, are increasingly used in recent preclinical immunotherapy studies and represent a remarkably unprecedented tool in this field. In this review, we describe, summarize, and discuss the recent advances of humanized mouse models used for cancer immunotherapy research and the challenges faced during their establishment. We also highlight the lack of preclinical studies using this model for radiotherapy-based research and argue that it can be a great asset to understand and answer many open questions around radiation therapy such as its presumed associated "abscopal effect".

摘要

免疫检查点抑制剂免疫疗法为癌症治疗开辟了新视野。新型免疫疗法或未探索的联合治疗方案的临床试验要么需要数年时间来开发,要么根本无法进行,比如对于预期寿命有限的癌症患者就是这种情况。因此,迫切需要能快速且安全地更好理解潜在机制、药物动力学和毒性,从而筛选出最佳治疗方案并转化到临床的临床前模型。能够同时承载人类免疫系统和人类肿瘤的人源化小鼠,在最近的临床前免疫疗法研究中越来越多地被使用,是该领域一项非常前所未有的工具。在这篇综述中,我们描述、总结并讨论了用于癌症免疫疗法研究的人源化小鼠模型的最新进展以及建立过程中面临的挑战。我们还强调了缺乏使用该模型进行基于放疗的研究的临床前研究,并认为它对于理解和回答许多围绕放射治疗的悬而未决的问题(如推测的相关“远隔效应”)可能是一项巨大的资产。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e7d/8636317/d62943497c54/fonc-11-784947-g001.jpg

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