Title: “Engineered Immune Cell Consortium”
Wilson Wong, PhD – BME (Advisor, Chair)
Allyson Sgro, PhD – BME
Trevor Siggers, PhD – Biology
The endogenous immune system is a complex consortium of cells which must interact to effectively detect and respond to threats. Communication between cells, either through direct contact or by secreted chemokines and cytokines, is integral to the immune system’s function. The ability to rewire these communications and program coordinated behavior in a multicellular immune network would open new doors in the field of cell therapies for cancer and other diseases, as well as enabling investigation of the design rules for cell consortia. Previous efforts to engineer population-level immune cell behavior have largely been limited to secretion of soluble factors, which are nonspecific actors and do not enable directed communication between specific cell types. Here, we develop a framework for engineering communication between engineered immune cells. We design and construct genetic circuits which enable the secretion of the adaptor molecule for a split CAR system in an activation-dependent manner, enabling modulation of the function of other user-specifed cells. This novel communication system enables programming of interactions between immune cells and provides a framework for the construction of complex cellular consortia.