Abstract: A method for inhibiting an immune response against a transplanted cell, tissue or organ is provided. In some embodiments, the method comprises administering an immunosuppressive cell to an individual that has received a transplant, wherein the immunosuppressive cell comprises a molecular circuit comprising the following components: (a) a binding-triggered transcriptional switch (BTTS) that recognizes a cell surface marker on a cell of the transplant; and one or any combination 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 (e) a nucleic acid encoding an ectonucleotidase, and wherein binding of the BTTS to the cell surface marker activates the protein(s) encoded by one or any combination of (b)-(e) by the immunosuppressive cell, thereby inhibiting an immune response against the transplanted organ or cell.

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.