A newly invented microfluid device can isolate potent T cells for cancer immunotherapy.
A new study, published in Advanced Healthcare Materials, has presented a novel microfluidic approach that can rapidly detect T cells that are most effective at attacking cancer cells.
A relatively new form of cancer immunotherapy, known as T cell receptor (TCR) therapy, isolates immune cells naturally occurring in the body and modifies them to enhance their ability to kill cancer cells. Currently, a lack of strategies for selecting potent T cells meant that none have gained clinical approval.
Researchers at Imperial College London have invented a device, which can be used to rapidly accelerate the clinical development of new T cell-based cancer immunotherapy.
The researchers said, “These results demonstrate how microfluidic probing of cellular avidity may fast track the therapeutic T cell selection process and move us closer to precision cancer immunotherapy.”
Accelerating T cell isolation
The main component of the device is a T cell-tumour cell interaction micro-channel region. Tumour cells attached to the device were subjected to ramping fluid shear stresses. At the highest experimental shear, researchers found that the tumour cells remained viable and remained adhered to the device.
The team found that the approach was capable of probing up to 10,000 T cell tumour cell interactions per run. It also recovered potent T cells with up to 100% purity from mixed populations of T cells within 30 minutes.
The authors wrote, “This platform could potentially accelerate the identification of suitable patient-specific neoantigen T cell candidates.”
Benefits of high avidity T cells
To test physiological activity of high avidity T cells, the team probed for intracellular calcium, a signalling indicator during T cell activation. High T cell avidity correlated with greater T cell activation.
Lastly, researchers examined the difference in immunological synapse formation and cytokine secretion in T cells of varying avidities. By measuring fluorescent intensity of a gap junction protein, Connexin-43, researchers found that higher avidity T cells expressed significantly higher levels of Connexin-43 accumulation. IFN-y levels were also obtained downstream from the outlet reservoir and scientists found that higher avidity T cells secreted greater levels of the cytokine.
Overall, this strategy has the potential to accelerate the isolation of optimal T cell clones providing promising applications in precision cancer medicine.
Dr Simon Hepworth, Director of Enterprise at Imperial said in Imperial College News, “In comparison to current techniques, this device has the potential to accelerate the clinical development of a whole range of innovative immunotherapies.”
Written by Harry Yuen, Science Writer Intern
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