Researchers grow immune cells with more targeted cancer-fighting abilities

Lymph nodes, considered the command centers of our immune system, often get swollen and stiff when fighting infection. Now, a UC Berkeley-led team of researchers has discovered that this mechanical change may help instruct our immune system to fight disease. Their findings could lead to a new method for manufacturing immune cells that maximizes their cancer-cell killing abilities while reducing side effects.

In a study recently published in Advanced Materials, the researchers investigated how immune cells respond to different mechanical environments. They exposed T cells, or lymphocytes, to hydrogels with varying levels of stiffness, mimicking the surface of a natural lymph node. Upon testing the immune cells’ cancer-fighting abilities, the researchers found that cells activated on stiff materials were more effective at killing target cancer cells, but cells activated on softer materials were more precise killers.

“Our findings suggest that the stiffening of lymph nodes is a way to activate immune cells to respond aggressively to serious infections or threats,” said Derfogail Delcassian, assistant professor of bioengineering and the study’s principal investigator. “We also showed that a ‘soft activation’ approach can help us make T cells that hit the right target, and only the right target, with fewer side effects.”

According to Delcassian, T cell and CAR-T cell therapies are currently manufactured using a “stiff activation” approach. These immune cells can sometimes be too aggressive and attack off-target cells, causing hyperinflammation and other side effects for patients. In addition, while super-aggressive T cells are desirable for treating cancer, when used to treat autoimmune diseases, they can worsen the condition.

“Using this system, we can now manufacture immune cells with more controlled activation levels,” said Delcassian. “This will make T cell and CAR-T cell therapies suitable for a wider range of diseases and may limit off-target side effects in patients.”

This technology is now being further developed for commercial use at UC Berkeley’s Bakar Bio Labs incubator.

In addition to Delcassian, coauthors of this study include Niroshan Anandasivam, Rabia Ali, Lordean Gustinvil and Matthew J. Rosenwasser, all from UC Berkeley’s Department of Bioengineering, and Iain Dunlop, Department of Materials, Imperial College, London.

This research was supported by the National Science Foundation, the Wagner Family Foundation Trust and the HS Chau WIES program.