Building Synthetic Immunity

  The success of engineered T cells for cancer therapy is revealing new opportunities to design immune cells for broad cancer applications. In this seminar, I will first present our work on displaying protease-activatable receptors on T cells to create a measurement tool for mapping the cancer degradome across various cancer types and tissues. I will highlight how this activity-based atlas can be harnessed for the design of ultrasensitive biosensors with improved detection limits and specificity compared to conventional blood biomarkers. In the second half of the seminar, I will share our strategies to overcome the challenges of solid tumor therapy with CAR T cells. These include the design of thermal gene switches to control the intratumoral production of immune potentiators, synthetic antigens to sensitize tumors to cell killing, and antigen-specific in vivo cell engineering. Taken together, our work illustrates how bioengineering can drive the development of improved tools for cancer detection and treatment.