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评估神经胶质瘤靶向免疫疗法的临床前模型。

Pre-clinical models for evaluating glioma targeted immunotherapies.

机构信息

School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United States.

出版信息

Front Immunol. 2023 Jan 9;13:1092399. doi: 10.3389/fimmu.2022.1092399. eCollection 2022.

Abstract

Gliomas have an extremely poor prognosis in both adult and pediatric patient populations as these tumors are known to grow aggressively and respond poorly to standard of care treatment. Currently, treatment for gliomas involves surgical resection followed by chemoradiation therapy. However, some gliomas, such as diffuse midline glioma, have more limited treatment options such as radiotherapy alone. Even with these interventions, the prognosis for those diagnosed with a glioma remains poor. Immunotherapy is highly effective for some cancers and there is great interest in the development of effective immunotherapies for the treatment of gliomas. Clinical trials evaluating the efficacy of immunotherapies targeted to gliomas have largely failed to date, and we believe this is partially due to the poor choice in pre-clinical mouse models that are used to evaluate these immunotherapies. A key consideration in evaluating new immunotherapies is the selection of pre-clinical models that mimic the glioma-immune response in humans. Multiple pre-clinical options are currently available, each one with their own benefits and limitations. Informed selection of pre-clinical models for testing can facilitate translation of more promising immunotherapies in the clinical setting. In this review we plan to present glioma cell lines and mouse models, as well as alternatives to mouse models, that are available for pre-clinical glioma immunotherapy studies. We plan to discuss considerations of model selection that should be made for future studies as we hope this review can serve as a guide for investigators as they choose which model is best suited for their study.

摘要

神经胶质瘤在成年和儿童患者中预后极差,因为这些肿瘤生长迅速,对标准治疗反应不佳。目前,神经胶质瘤的治疗包括手术切除,然后进行放化疗。然而,一些神经胶质瘤,如弥漫性中线神经胶质瘤,治疗选择更为有限,如仅放疗。即使进行这些干预,诊断为神经胶质瘤的患者预后仍然很差。免疫疗法对某些癌症非常有效,因此人们非常关注开发有效的免疫疗法来治疗神经胶质瘤。评估针对神经胶质瘤的免疫疗法疗效的临床试验迄今为止大多失败了,我们认为这部分是由于在用于评估这些免疫疗法的临床前小鼠模型选择不当。评估新免疫疗法的一个关键考虑因素是选择模拟人类神经胶质瘤-免疫反应的临床前模型。目前有多种临床前选择,每种选择都有其自身的优点和局限性。在本综述中,我们计划介绍神经胶质瘤细胞系和小鼠模型,以及替代小鼠模型的选择,这些选择可用于临床前神经胶质瘤免疫治疗研究。我们计划讨论未来研究中应考虑的模型选择问题,因为我们希望本综述可以为研究人员提供指导,帮助他们选择最适合其研究的模型。

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