Microfluidic Model for Evaluation of Immune Checkpoint Inhibitors in Human Tumors

Area of Science:

• Biomedical Engineering
• Immunology
• Oncology

Background:

• Developing effective immunotherapies requires understanding drug response within the tumor microenvironment.
• Current methods often lack the ability to assess real-time responses in patient-specific tumor tissues.

Purpose of the Study:

• To demonstrate a novel technology for real-time monitoring of lymphocyte response to immunotherapeutic agents in biopsied tumor tissue.
• To establish a platform for drug development and precision medicine in immunotherapy.

Main Methods:

• A microfluidic tumor trapping device was fabricated using a novel 3D-printed, transparent, noncytotoxic substrate (Pro3dure GR-10).
• The device sustains biopsied tumor fragment viability under dynamic perfusion for at least 72 hours.
• Confocal microscopy with fluorescent tracers enabled real-time monitoring of tumor response to various immunotherapies.

Main Results:

• The 3D-printed device successfully maintained tumor tissue viability and allowed simultaneous drug treatment administration.
• Real-time monitoring of resident lymphocyte populations within the tumor microenvironment was achieved.
• This platform demonstrated the ability to test immune checkpoint inhibitors on human tumor fragments in a dynamic perfusion system.

Conclusions:

• This technology represents the first real-time monitoring system for immunotherapy response in perfused human tumor microenvironments.
• The developed platform offers a valuable tool for drug development and personalized immunotherapy strategies.
• This methodology aids in modeling and analyzing tumor response for improved prediction of patient-specific immunotherapy efficacy.