Artificial 'cells' boost immune response

Source: Yale University

Using artificial cell-like particles, Yale University biomedical engineers have devised a rapid and efficient way to produce a 45-fold enhancement of T cell activation and expansion.

The artificial cells, developed by Tarek Fahmy, assistant professor of biomedical engineering at Yale and his graduate student Erin Steenblock, are made of a material commonly used for biodegradable sutures.

The authors say that the new method is the first "off-the-shelf" antigen-presenting artificial cell that can be tuned to target a specific disease or infection.

"This procedure is likely to make it to the clinic rapidly," Fahmy said. "All of the materials we use are natural, biodegradable and already have FDA approval."

Cancer, viral infections and autoimmune diseases have responded to immunotherapy that boosts a patient's own antigen-specific T cells. In those previous procedures, a patient's immune cells were harvested and then exposed to cells that stimulate the activation and proliferation of antigen-specific T-cells. The "boosted" immune cells were then infused back into the patient to attack the disease.

Limitations of these procedures include costly and tedious custom isolation of cells for individual patients and the risk of adverse reaction to foreign cells, according to the Yale researchers. They also pointed to difficulty in obtaining and maintaining sufficient numbers of activated T-cells for effective therapeutic response.

In the new system, the outer surface of each particle is covered in universal adaptor molecules that serve as attachment points for antigens and for stimulatory molecules. Inside of each particle, there are slowly released cytokines that further stimulate the activated T-cells to proliferate to as much as 45 times their original number.

"Our process introduces several important improvements," Steenblock said. "First, the universal surface adaptors allow us to add a span of targeting antigen and co-stimulatory molecules.

"We can also create a sustained release of encapsulated cytokines. These enhancements mimic the natural binding and signalling events that lead to T-cell proliferation in the body. It also causes a fast and effective stimulation of the patient's T-cells - particularly T-cells of the cytotoxic type important for eradicating cancer."

The researchers reported their findings in an advance online report in the journal Molecular Therapy.