Engineering the Next Generation of Immune Cell Therapeutics

Cells of the immune system play a unique role in the body, detecting and responding to pathologic insults and deviations. As such, these cells have exceptional properties. They are semiautonomous, often moving freely about the body to survey and infiltrate diverse tissues. Immune cells act as general sensor-response agents, detecting local problems and responding in diverse ways—sometimes executing powerful targeted actions like cell killing and phagocytosis, and at other times taking more subtle but broad actions, like secreting cytokines and chemokines that communicate with and mobilize other cells (Figure 1). Equally important, immune cells are relatively easy to remove, modify, and transfer back into a patient. 

Given these unique properties, immune cells provide a remarkable platform for interfacing with and treating disease. There are many complex diseases, such as cancer and autoimmunity that our natural immune systems either cannot handle or pathologically contribute to. Thus, there is a strong rationale to engineer new disease sensing and response behaviors in immune cells, especially given recent powerful advances in synthetic biology and genome editing, which give us unprecedented ability to modify and engineer cellular functions.

Synthetic immunology is an emerging strategy that applies the tools and approaches of systems and synthetic biology to reprogram and enhance the function of immune cells, thus also rewiring the overall capabilities of our immune system. 

In the Roybal Lab, we harness the tools of synthetic and chemical biology to enhance the therapeutic potential of engineered immune cells. We take a comprehensive approach to cellular engineering by developing new synthetic receptors, signal transduction cascades, and cellular response programs to enhance the safety and effectiveness of adoptive cell therapies (Figure 2). We also study the logic of natural cellular signaling systems, and the underlying principles of cellular communication and collective cell behavior during an immune response. These interests are complementary as cell engineering is often informed by knowledge obtained from studying natural mechanisms of cell regulation refined by evolution.