Microfluidic Model for Evaluation of Immune Checkpoint Inhibitors in Human Tumors.

Abstract

Presented is the first demonstration of real-time monitoring of the response of resident lymphocyte populations in biopsied tumor tissue to immunotherapeutic agents in a perfused tumor microenvironment. This technology comprises a microfluidic tumor trapping device constructed from a novel 3D-printed, transparent, noncytotoxic substrate. The 3D-printed device sustains viability of biopsied tissue fragments under dynamic perfusion for at least 72 h while enabling simultaneous administration of various drug treatments, illustrating a useful tool for drug development and precision medicine for immunotherapy. Confocal microscopy of the tumor tissue and resident lymphocytes in the presence of fluorescent tracers provides real-time monitoring of tumor response to various immunotherapies. Devices are additively manufactured in Pro3dure GR-10 (i.e., a relatively new, high-resolution stereolithographic resin with properties suitable for biomedical applications), allowing integration of a set of finely featured functional components into a monolithically constructed platform. The presented platform comprises a new methodology for modeling and analyzing tumor response for the improved prediction of patient-specific immunotherapy efficacy. It is acknowledged that this is the first report of human tumor fragments cultured in a dynamic perfusion system capable of testing the effect of circulating immune checkpoint inhibitors on resident tumor-infiltrating lymphocytes.