Synthetic feedback control of TCR signaling to guide T cell development in vitro

T cells are an important component of our body’s adaptive immune system, helping to identify and overcome diverse diseases. An emerging treatment for cancer, viral infections, and other diseases is to engineer patient’s T cells to recognize and respond to diseased cells. However, because of the reliance on patient-derived T cells, such treatments are highly expensive. To lower costs and increase accessibility to T cell therapies, our laboratory is developing methods to generate T cells from an unlimited and readily-available source: human pluripotent stem cells. Pluripotent stem cells give rise to every cell in our bodies, including T cells, and can be grown indefinitely in laboratory settings. Our current process for producing T cells from stem cells has made great progress, but lacks control over key parameters such as whether the T cells will become “helper” cells that stimulate the immune system or “cytotoxic” cells that directly kill diseased cells, and if they will provide long-term memory or have strong, short-term effects. In this project, I will genetically engineer stem cells such that we can produce T cells with these diverse properties on-demand, thereby enabling the next generation of off-the-shelf T cell therapies.