4.8 Article

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

Journal

SMALL
Volume 17, Issue 7, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202004282

Keywords

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

Funding

  1. National Institutes of Health [CA214411]

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A miniaturized bioreactor system known as iHOC has been developed to model tumor-immune interactions and test the effect of anti-PD-1 antibodies on cancer spheroids and T cells. The system allows for facile monitoring of T cell inhibition and reactivation through measuring IL-2 concentration, providing a high-throughput platform for studying cancer-immune interactions in response to immunotherapy.
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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