Researchers from the Terasaki Institute for Biomedical Innovation (TIBI) have designed a microwell-based chip to test immunotherapy drugs. They started by culturing spherical aggregates of breast cancer cells in a custom-fabricated chip with conical microwells. These microwells were designed for growth and stability f the cellular spheres.
"The features of our microwell-based chip is the key to our successful development of an immunoactive tissue model," said Wujin Sun, Ph.D., from the Terasaki Institute's team. "The chip's transparency allows for direct microscopic observation. And its design allows for high-volume testing, which lends itself well to the rapid screening of immunotherapeutic drugs."
In order to test the effectiveness of checkpoint inhibitor drugs in activating T-cells' anti-tumor response, the team next considered how a T-cell normally behaves during activation. When a T-cell is stimulated to attack cellular invaders, it secretes proteins called cytokines, which mobilize other immune cells to the invasion site and stimulates the cells to multiply and destroy the invaders. Measurement of these cytokines can therefore indicate the level of a T-cell's activation.
The TIBI researchers were able to design methods for characterizing the interaction between tumor and immune cells and for rapid, high-volume and clinically-relevant ways to screen immunotherapeutic drugs against tumor cells. The microwell chip and its related apparatus can also be utilized for other types of tumor cells.
"Bringing ways to optimize clinical decisions and personalized medicine for patients is a top goal at our institute," said Ali Khademhosseini, Ph.D., director and CEO of the Terasaki Institute. "This work is a significant step towards achieving that goal in the realm of cancer immunotherapy."