Yale Bulletin and Calendar

March 7, 2008|Volume 36, Number 21|Two-Week Issue

Yale-developed artificial cell helps
immune system fight cancer

Using artificial cell-like particles, Yale biomedical engineers have devised a rapid and efficient way to enhance the body’s ability to fight cancer and infectious diseases, according to an online report in Molecular Therapy.

The artificial cells created by the Yale scientists produce a 45-fold increase in a patient’s number of T cells, which play an important role in the body’s immune response. T cells are activated by molecules called antigens to recognize and fight off a specific disease.

Tarek Fahmy, assistant professor of biomedical engineering at Yale, and his graduate student, Erin Steenblock, created the cells from 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,” says senior author Fahmy. “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 procedures, a patient’s immune cells are harvested and then exposed to cells that stimulate the activation and proliferation of antigen-specific T-cells. The “boosted” immune cells are then infused back into the patient to attack the disease.

The disadvantages of these procedures, say the Yale researchers, include the need for costly and tedious custom isolation of cells for individual patients and the risk of adverse reaction to foreign cells. In addition, they add, it is difficult to obtain and maintain 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 other molecules that stimulate immune response. Inside of each particle, there are slowly released cytokines (cell-signalling compounds) that further stimulate the activated T-cells to increase up to 45 times their original number.

“Our process introduces several important improvements,” says lead author Steenblock. “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 signaling 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.”

Fahmy adds, “Safe and efficient T-cell stimulation and proliferation in response to specific antigens is a goal of immunotherapy against infectious disease and cancer. Our ability to manipulate this response so rapidly and naturally with an ‘off-the-shelf’ reproducible biomaterial is a big step forward.”

Fahmy was recently awarded a five-year National Science Foundation (NSF) Career Award for work on this process and ways of engineering biomaterials to manipulate immune responses to fight cancer and other diseases.

According to the NSF, devices such as these offer ease and flexibility in targeting different types of T-cells, and are expected to lead to state-of-the-art improvements in the preparation of a new generation of therapeutic systems.

The U.S. Department of Homeland Security provided partial funding for this work.

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