Cancer immunotherapy target of WashU mechanobiology research

One of the latest treatments for cancer is immunotherapy, which involves genetically modifying a patient’s own immune cells to fight tumor growth and spread. An engineer and an immunology researcher at Washington University in St. Louis are collaborating to find a better way to prepare and treat these immune cells to maximize their effectiveness in patients.

Amit Pathak, assistant professor of mechanical engineering & materials science in the School of Engineering & Applied Science who specializes in mechanobiology, and Eynav Yafit Klechevsky, assistant professor of pathology & immunology in the School of Medicine, have received a three-year, $610,000 Trailblazer Award from the National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering.

In immunotherapy, researchers extract T cells — immune cells that fight infection in the body —from a patient’s blood, manipulate them in a lab to recognize cancer cells, then return them to the patient to destroy the cancer cells.

Pathak, who studies how cells’ behavior and properties can be modified by the type of material the cells sit on, or its microenvironment, will work with Klechevsky to modify the microenvironment in which T cells are manipulated in the lab to mimic the biomechanical properties of dendritic cells, which are Klechevsky’s focus of research. Dendritic cells are found in most of the body’s tissues and process foreign substances or toxins known as antigens and present them to T cells to promote immunity.

T cells seek soft environments because the molecules can more easily cluster around them, while tumors prefer stiff environments because they can exert more force and grow more quickly, Pathak said. Currently, researchers grow T cells on plastic surfaces, which are stiff, but allows such cells to multiply by the thousands cheaply and quickly. Pathak wants to treat the cells in a soft environment using synthetic dendritic cells that more closely represents the body.

“What we hope to achieve is to get the T cells from the patient, then make a platform which will have soft materials and a coating of patient-specific antigens and other molecules that mimic dendritic cells,” Pathak said. “We would put the T-cells in the patient-tailored environment and expand them to make more of them, then put them back in the body to treat the tumor.”

Pathak and Klechevsky have already filed a provisional patent on their platform working with the university’s Office of Technology Management.

Although immunotherapy is already being used, it treats all tumors the same way, although they are different, Pathak says.

“If the tumor is in the brain, it’s softer than when it’s in breast or bone,” Pathak said. “These T cells are experiencing all of these different heterogeneities, but how they process these environments is unknown. This is something engineering and mechanobiology can address.”

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