The Biotechnology Training Program is pleased to present the following seminar by Milos Simic:

Programming tissue-sensing T cells to deliver therapies to the brain

Central nervous system (CNS) disorders are a leading cause of global disease burden and high economic cost, estimated at $800 billion per year in the US. Current systemic treatments have poor CNS penetration at therapeutic doses and numerous side effects. An ideal treatment should localize its action to the affected area. Immune cells could be engineered to deliver therapeutic payloads to specific tissues, such as the CNS. To engineer immune cells that target the 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, such as 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 and anatomically targeted manner.

Milos Simic is a synthetic immunologist developing cell-based delivery platforms for brain diseases. His research focuses on combining cell engineering and synthetic biology to understand and treat brain diseases. Simic and his colleagues pioneered the concept of a programmable "tissue GPS" for cells, allowing a cell to precisely know where it is in the body to locally execute a predefined program. This concept is currently being applied for the treatment of brain cancers, with a potential clinical trial underway, as well as the treatment of neuroinflammation. He is eager to expand those concepts to treat other diseases of the brain, including neurodegeneration.