Li Zhuo, Yang Xiao, Zhang Yilu, Yang Xiaolong, Cui Xinxin, Zhang Yanjuan, Gong Wenfeng, Bai Huichen, Liu Ning, Tang Zhiyu, Guo Mingming, Li Kang, Zhang Tong, Wang Lai, Song Xiaomin
BeiGene (Beijing) Co., Ltd.
BeiGene (Beijing) Co., Ltd.;
J Vis Exp. 2019 Aug 15(150). doi: 10.3791/59679.
The discovery and development of immuno-oncology (I-O) therapy in recent years represents a milestone in the treatment of cancer. However, treatment challenges persist. Robust and disease-relevant animal models are vital resources for continued preclinical research and development in order to address a range of additional immune checkpoints. Here, we describe a human peripheral blood mononuclear cell (PBMC) - based humanized xenograft model. BGB-A317 (Tislelizumab), an investigational humanized anti-PD-1 antibody in late-stage clinical development, is used as an example to discuss platform set-up, model characterization and drug efficacy evaluations. These humanized mice support the growth of most human tumors tested, thus allowing the assessment of I-O therapies in the context of both human immunity and human cancers. Once established, our model is comparatively time- and cost-effective, and usually yield highly reproducible results. We suggest that the protocol outlined in this article could serve as a general guideline for establishing mouse models reconstituted with human PBMC and tumors for I-O research.
近年来免疫肿瘤学（I-O）疗法的发现和发展是癌症治疗领域的一个里程碑。然而，治疗挑战依然存在。强大且与疾病相关的动物模型是持续进行临床前研究和开发的重要资源，以便攻克一系列其他免疫检查点。在此，我们描述一种基于人外周血单核细胞（PBMC）的人源化异种移植模型。以处于临床开发后期的研究性人源化抗PD-1抗体BGB-A317（替雷利珠单抗）为例，讨论平台搭建、模型表征及药物疗效评估。这些人源化小鼠支持所测试的大多数人类肿瘤的生长，从而能够在人类免疫和人类癌症的背景下评估I-O疗法。一旦建立，我们的模型相对节省时间和成本，并且通常能产生高度可重复的结果。我们建议本文概述的方案可作为建立用人PBMC和肿瘤重建的小鼠模型用于I-O研究的通用指南。
