Evaluating immune response in vitro in a relevant microenvironment: a high-throughput microfluidic model for clinical...

Area of Science:

• Oncology
• Biotechnology
• Drug Discovery

Background:

• Clinically relevant models are crucial for monitoring cancer progression and treatment responses.
• Tumor cell plasticity, including invasiveness and immune evasion, presents challenges in cancer therapy.
• Identifying key pathways is essential for designing effective combination inhibitor strategies.

Purpose of the Study:

• To introduce a novel microfluidic device for functional screening of pharmaceutical compounds in breast cancer.
• To evaluate the device's utility for assessing drug treatments, including combinations, and predicting personalized medicine outcomes.

Main Methods:

• Development of a microfluidic chip with 150 droplet-trapping microwells for multi-chip and multi-treatment settings.
• Validation using established cell lines and clinical drugs, followed by preclinical experiments with patient-derived xenografts (PDX) and tumoroids.
• Incorporation of tumor-isolated lymphocytes into tumoroids for immune response assessment in proof-of-concept studies.

Main Results:

• The microfluidic system demonstrated relevance for screening a large number of drugs, diverse doses, and multiple drug combinations.
• Successful validation with clinical cell lines and drugs, alongside preclinical experiments using PDX and tumoroids.
• Proof-of-concept experiments showed the feasibility of incorporating immune cells for comprehensive response evaluation.

Conclusions:

• The developed microfluidic methodology is highly relevant for high-throughput drug screening and personalized medicine applications in oncology.
• This technology facilitates the evaluation of drug combinations for optimizing cancer treatment strategies.
• The chip's potential for rapid, two-week preclinical assays supports personalized medicine by identifying optimized treatment plans with clinical relevance.