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

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

doi:10.1002/smll.202004282

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

Small. 2021 Feb;17(7):e2004282. doi: 10.1002/smll.202004282. Epub 2021 Jan 27.

Authors

Xing Jiang^{1

2}, Li Ren^{1

3}, Peyton Tebon¹, Canran Wang^{1

4}, Xingwu Zhou¹, Moyuan Qu^{1

5}, Jixiang Zhu^{1

6}, Haonan Ling^{1

7}, Shiming Zhang^{1

8}, Yumeng Xue^{1

9}, Qingzhi Wu^{1

10}, Praveen Bandaru¹, Junmin Lee^{1

11}, Han-Jun Kim^{1

11}, Samad Ahadian^{1

11}, Nureddin Ashammakhi¹, Mehmet R Dokmeci^{1

11}, Jinhui Wu¹², Zhen Gu¹, Wujin Sun^{1

11}, Ali Khademhosseini^{1

11}

Affiliations

¹ Department of Bioengineering, Center for Minimally Invasive Therapeutics, California Nanosystems Instituste, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
² School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
³ Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China.
⁴ Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
⁵ The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, Zhejiang, 310006, China.
⁶ Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
⁷ Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁸ Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong.
⁹ Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710000, China.
¹⁰ State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, 430070, China.
¹¹ Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90064, USA.
¹² State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University & School of Life Sciences, Nanjing University, Nanjing, 210093, China.

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.

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

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Humans
Immune Checkpoint Inhibitors*
Immunotherapy
Lab-On-A-Chip Devices
Neoplasms* / drug therapy

Substances

Immune Checkpoint Inhibitors

Grants and funding

U01 CA214411/CA/NCI NIH HHS/United States