Cancer-on-a-Chip for Modeling Immune Checkpoint Inhibitor and Tumor Interactions

用于模拟免疫检查点抑制剂和肿瘤相互作用的癌症芯片

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作者:Xing Jiang, Li Ren, Peyton Tebon, Canran Wang, Xingwu Zhou, Moyuan Qu, Jixiang Zhu, Haonan Ling, Shiming Zhang, Yumeng Xue, Qingzhi Wu, Praveen Bandaru, Junmin Lee, Han-Jun Kim, Samad Ahadian, Nureddin Ashammakhi, Mehmet R Dokmeci, Jinhui Wu, Zhen Gu, Wujin Sun, Ali Khademhosseini

Abstract

Cancer immunotherapies, including immune checkpoint inhibitor (ICI)-based therapies, have revolutionized cancer treatment. However, patient response to ICIs is highly variable, necessitating the development of methods to quickly assess efficacy. In this study, an array of miniaturized bioreactors has been developed to model tumor-immune interactions. This immunotherapeutic high-throughput observation chamber (iHOC) is designed to test the effect of anti-PD-1 antibodies on cancer spheroid (MDA-MB-231, PD-L1+) and T cell (Jurkat) interactions. This system facilitates facile monitoring of T cell inhibition and reactivation using metrics such as tumor infiltration and interleukin-2 (IL-2) secretion. Status of the tumor-immune interactions can be easily captured within the iHOC by measuring IL-2 concentration using a micropillar array where sensitive, quantitative detection is allowed after antibody coating on the surface of array. The iHOC is a platform that can be used to model and monitor cancer-immune interactions in response to immunotherapy in a high-throughput manner.

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