Stanford Cancer Institute

SCI Innovation Awardee

October 2023

Kyle Daniels, PhD, assistant professor of genetics, was awarded a $50,000 SCI Innovation Award for his proposal titled “High-throughput engineering of receptors and signaling adapters to program anti-tumor macrophages.” Daniels uses synthetic biology to engineer gene circuits and control cell functions. He is specifically interested in engineering blood and immune cells to regulate their activity and promote anti-cancer responses.

Synthetic biology innovations have made it possible to engineer immune cells to find and attack cancer cells. One way this is done is to produce immune cells expressing engineered receptors that specifically bind proteins (known as antigens) found only on the surface of tumor cells. The immune receptors are termed chimeric antigen receptors(CARs). This technology has been used to modify different types of immune cells, including macrophages, cells that engulf and kill their targets. But these so-called “CAR-M” cells have some weaknesses. They do not efficiently recognize cancer cells expressing low levels of antigen, they don’t last long in the body, and their ability to‘eat cells is inhibited by molecular signals on the surface of cancer cells. Daniels has devised an approach to overcome these challenges. With the support of the SCI Innovation Award, he will test a range of modified receptors to understand how different receptor segments impact receptor activity and will identify combinations that improve macrophage survival and ability to recognize and kill tumor cells. These new CAR-Ms will advance both biology and therapeutics. They will provide new insights into macrophage function and behavior and enable the design of more effective CAR-Ms for the treatment of cancer.