PME Special Seminar - Dr. Milos Simic

Programming Tissue-Sensing T Cells to Deliver Therapies to the Brain

Immune cells could potentially be engineered to deliver therapeutic payloads to specific tissues. To engineer immune cells that target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including unique components of the CNS extracellular matrix and neural/glial cell surface molecules. We engineered synNotch receptors to detect these antigens and used them to program T cells that induce the expression of diverse payloads. CNS-targeted T cells inducing chimeric antigen receptor (CAR) expression efficiently cleared primary and secondary brain tumor xenografts, without killing cross-reactive cells outside the brain. Conversely, CNS-targeted cells delivering immuno-suppressive payloads, like the cytokine interleukin-10 (IL-10), ameliorated symptoms of a mouse model of neuroinflammatory disease. Thus, CNS-sensing cells provide a flexible new platform to address diverse CNS disorders in a precise, anatomically targeted manner.