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免疫肿瘤学疗法开发的临床前模型。

Preclinical models for development of immune-oncology therapies.

作者信息

Wang Yufei, Shelton Sarah E, Kastrunes Gabriella, Barbie David A, Freeman Gordon J, Marasco Wayne A

机构信息

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA and Harvard Medical School, Boston, MA 02115, USA.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Immuno-oncol Insights. 2022;3(8):379-398. doi: 10.18609/ioi.2022.41. Epub 2022 Sep 26.

Abstract

Immunotherapy has demonstrated great success in clinical treatment, especially for cancer care. Here we review preclinical models, including cell lines, three dimensional (3D) cultures, and mouse models to support the need for tools enabling the development of novel immune-oncology (I-O) therapies. While studies have the advantage of being relatively simpler, faster, and higher throughput than models, they must be designed carefully to recapitulate the biological conditions that influence drug efficacy. The growing prevalence of 3D and models has enabled screening and mechanistic studies in more complex, tissue-like environments containing multiple interacting cell types. On the other hand, syngeneic mouse models have been instrumental in the historical development of immunotherapies and remain an important tool in drug development, despite lacking fidelity to certain aspects of human physiology and pathology. Xenograft and humanized mouse models address some of these challenges, yet present limitations of their own. Successful development and translation of new I-O therapies will likely require thoughtful combination of several of these preclinical models, and we aim to help research and development scientists utilize the appropriate tools and technologies to facilitate rapid transition from preclinical evaluation to clinical trials.

摘要

免疫疗法在临床治疗中已显示出巨大成功,尤其是在癌症治疗方面。在此,我们回顾临床前模型,包括细胞系、三维(3D)培养物和小鼠模型,以支持开发新型免疫肿瘤学(I-O)疗法所需工具的必要性。虽然细胞系研究具有相对简单、快速和高通量的优势,但与动物模型相比,必须精心设计以重现影响药物疗效的生物学条件。3D培养物和类器官模型的日益普及,使得在包含多种相互作用细胞类型的更复杂、类似组织的环境中进行筛选和机制研究成为可能。另一方面,同基因小鼠模型在免疫疗法的历史发展中发挥了重要作用,尽管在人类生理学和病理学的某些方面缺乏逼真度,但仍然是药物开发中的重要工具。异种移植和人源化小鼠模型解决了其中一些挑战,但也有其自身的局限性。新的I-O疗法的成功开发和转化可能需要对这些临床前模型中的几种进行深思熟虑的组合,我们旨在帮助研发科学家利用适当的工具和技术,促进从临床前评估到临床试验的快速过渡。

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