Microfluidic T Cell Selection by Cellular Avidity.

Area of Science:

• Immunology
• Biotechnology
• Cancer Research

Background:

• T cell receptor (TCR) T cell therapies face challenges in clinical approval.
• Current T cell selection methods, like peptide multimers, measure affinity but not cellular avidity or activation markers.
• Lack of robust selection strategies hinders the development of effective T cell therapies.

Purpose of the Study:

• To develop a novel microfluidic approach for identifying and recovering potent T cell clones.
• To assess cellular avidity between T cells and tumor cells as a measure of potency.
• To accelerate the selection process for precision cancer immunotherapy.

Main Methods:

• A microfluidic fluid shear stress-based platform was developed.
• The method probes T cell-tumor cell interactions to measure cellular avidity.
• High-throughput screening of up to 10,000 interactions per run was performed.

Main Results:

• The microfluidic approach rapidly identifies and recovers potent T cells based on cellular avidity.
• High-avidity T cells were recovered with up to 100% purity within 30 minutes.
• Recovered T cells maintained markers of cytotoxicity, activation, and avidity upon re-exposure to tumor cells.

Conclusions:

• Microfluidic probing of cellular avidity offers a fast and efficient method for T cell selection.
• This approach can significantly expedite the development of T cell therapies for cancer.
• The findings pave the way for enhanced precision cancer immunotherapy.