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

被引：59

作者：

Jiang, Xing ^{[1
,2
]}

Ren, Li ^{[1
,3
]}

Tebon, Peyton ^{[1
]}

Wang, Canran ^{[1
,4
]}

Zhou, Xingwu ^{[1
]}

Qu, Moyuan ^{[1
,5
,6
]}

Zhu, Jixiang ^{[1
,7
]}

Ling, Haonan ^{[1
,8
]}

Zhang, Shiming ^{[1
,9
]}

Xue, Yumeng ^{[1
,10
]}

Wu, Qingzhi ^{[1
,11
]}

Bandaru, Praveen ^{[1
]}

Lee, Junmin ^{[1
,12
]}

Kim, Han-Jun ^{[1
,12
]}

Ahadian, Samad ^{[1
,12
]}

Ashammakhi, Nureddin ^{[1
]}

Dokmeci, Mehmet R. ^{[1
,12
]}

Wu, Jinhui ^{[13
,14
]}

Gu, Zhen ^{[1
]}

Sun, Wujin ^{[1
,12
]}

Khademhosseini, Ali ^{[1
,12
]}

机构：

[1] Univ Calif Los Angeles, Calif Nanosyst Inst, Ctr Minimally Invas Therapeut, Dept Bioengn, Los Angeles, CA 90095 USA

[2] Nanjing Univ Chinese Med, Sch Nursing, Nanjing 210023, Peoples R China

[3] Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Biosci & Biotechnol, Xian 710072, Shaanxi, Peoples R China

[4] Shanghai Jiao Tong Univ, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai 200025, Peoples R China

[5] Zhejiang Univ, Sch Med, Sch Stomatol, Affiliated Hosp Stomatol, Hangzhou 310006, Zhejiang, Peoples R China

[6] Key Lab Oral Biomed Res Zhejiang Prov, Hangzhou 310006, Zhejiang, Peoples R China

[7] Guangzhou Med Univ, Sch Basic Med Sci, Dept Biomed Engn, Guangzhou 511436, Peoples R China

[8] Univ Calif Los Angeles, Dept Mech & Aerosp Engn, Los Angeles, CA 90095 USA

[9] Univ Hong Kong, Dept Elect & Elect Engn, Hong Kong, Peoples R China

[10] Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, Xian 710000, Peoples R China

[11] Wuhan Univ Technol, State Key Lab Adv Technol Mat Synth & Proc, Wuhan 430070, Peoples R China

[12] Terasaki Inst Biomed Innovat, Los Angeles, CA 90064 USA

[13] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Med, Nanjing 210093, Peoples R China

[14] Nanjing Univ, Sch Life Sci, Nanjing 210093, Peoples R China

来源：

SMALL | 2021年 / 17卷 / 07期

基金：

美国国家卫生研究院;

关键词：

cancer immunotherapy; cancer-on-a-chip; drug screening; high-throughput observation chamber; immune checkpoint inhibitors;

D O I：

10.1002/smll.202004282

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：10

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