1. A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research
- Author
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Mingming Guo, Ning Liu, Zhiyu Tang, Lai Wang, Yilu Zhang, Xiaolong Yang, Wenfeng Gong, Kang Li, Tong Zhang, Zhuo Li, Xinxin Cui, Xiao Yang, Xiaomin Song, Huichen Bai, and Yanjuan Zhang
- Subjects
0301 basic medicine ,medicine.medical_treatment ,General Chemical Engineering ,Programmed Cell Death 1 Receptor ,Context (language use) ,Mice, SCID ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,Efficacy ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Neoplasms ,medicine ,Animals ,Humans ,biology ,General Immunology and Microbiology ,business.industry ,General Neuroscience ,Antibodies, Monoclonal ,Cancer ,Immunotherapy ,medicine.disease ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,030104 developmental biology ,Leukocytes, Mononuclear ,biology.protein ,Cancer research ,Antibody ,business ,030215 immunology - Abstract
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.
- Published
- 2019
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