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
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