A major problem is the tumor microenvironment (TME), which is a mix of cells and molecules that can dampen immune responses. In most solid tumors, inhibitory signals dominate while helpful ones (that tell T cells to keep going) are weak or entirely absent. Since engineered T cells rely on these environmental cues to stay active and functional, they often fall short. This has led scientists to explore ways of building extra receptors into the T cells, so they can pick up tumor-specific signals and respond with added strength.

Researchers have tried to create receptors that can sense and react to the TME, but designing them has been difficult because building custom signaling proteins is a complex endeavor. Meanwhile, most current methods for doing so rely heavily on trial-and-error, which eventually makes it hard to control how these synthetic receptors will eventually behave when deployed against a tumor.