类有机物
生命银行
生物
胶质母细胞瘤
免疫疗法
嵌合抗原受体
癌症研究
癌症
计算生物学
生物信息学
神经科学
遗传学
作者
Fadi Jacob,Ryan Salinas,Daniel Y. Zhang,Phuong Nguyen,Jordan G. Schnoll,Samuel Zheng Hao Wong,Radhika Thokala,Saad Sheikh,Deeksha Saxena,Stefan Prokop,Di-ao Liu,Xuyu Qian,Dmitriy Petrov,Timothy Lucas,H. Isaac Chen,Jay F. Dorsey,Kimberly M. Christian,Zev A. Binder,MacLean P. Nasrallah,Steven Brem,Donald M. O’Rourke,Guo‐li Ming,Hongjun Song
出处
期刊:Cell
[Elsevier]
日期:2020-01-01
卷期号:180 (1): 188-204.e22
被引量:481
标识
DOI:10.1016/j.cell.2019.11.036
摘要
Glioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of parental tumors and require a prolonged generation time. Here, we report methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. GBOs can be generated quickly with high reliability and exhibit rapid, aggressive infiltration when transplanted into adult rodent brains. We further demonstrate the utility of GBOs to test personalized therapies by correlating GBO mutational profiles with responses to specific drugs and by modeling chimeric antigen receptor T cell immunotherapy. Our studies show that GBOs maintain many key features of glioblastomas and can be rapidly deployed to investigate patient-specific treatment strategies. Additionally, our live biobank establishes a rich resource for basic and translational glioblastoma research.
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