Engineering advanced logic and distributed computing in human CAR immune cells

The immune system's sophisticated network of cell types performs complex biocomputation. Reprogramming this system holds promise for treating diseases, as seen in CAR T-cell cancer therapy. However, most CAR designs lack computational features and coordinated reprogramming of multiple immune cell types. This study leverages the SUPRA CAR system to develop an inhibitory feature, achieving a three-input logic, demonstrating functionality in diverse immune cells. Inducible multicellular circuits, a kill switch, and a synthetic intercellular communication channel are also created. The simple split CAR design generates diverse, complex phenotypes, providing a foundation for engineering immune cell consortia with user-defined functionalities.

Jang Hwan Cho, Atsushi Okuma, Katri Sofjan, Seunghee Lee, James J. Collins, Wilson W. Wong