Abstract: This disclosure provides, among other things, an engineered immunosuppressive (e.g., CD4+) T cell comprising a molecular circuit comprising the following components: (a) a central nervous system (CNS)-specific binding-triggered transcriptional switch (BTTS); and (b) a nucleic acid encoding an anti-inflammatory payload, wherein binding of the BTTS to a marker on the surface of a target cell activates expression of the anti-inflammatory payload by the cell. A method of reducing inflammation in the brain of a subject is also provided.

Abstract: Provided herein is a synthetic immuno-suppressive cell that contains comprises a molecular circuit comprising the following components: (a) a binding-triggered transcriptional switch (BTTS); and one or both of: (b) a nucleic acid encoding a pro-inflammatory cytokine sink, (c) a nucleic acid encoding an anti-inflammatory cytokine, (d) a nucleic acid encoding an immune inhibitory receptor, or ligand thereof, and (c) a nucleic acid encoding an ectonucleotidase. In this circuit, binding of the BTTS to a marker on the surface of a target cell activates expression of one or any combination of (b)-(c) by the synthetic immuno-suppressive cell.

Abstract: Provided herein is a cell comprising a recombinant nucleic acid encoding a transmembrane protein that has an extracellular binding domain that specifically binds to a brain-selective extracellular antigen, e.g., MOG, CDH10, PTPRZ1 or NRCAM, wherein the cell does not comprise a nucleic acid encoding an antigen-specific therapeutic that binds to a killing antigen expressed by a glioblastoma.

Abstract: A method for treating a subject for glioblastoma is provided. In some embodiments, the method may comprise administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that, when bound to MOG, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.