Viral vectors for glioblastoma cell therapy

Abstract

This disclosure provides, among other things, a recombinant nucleic acid comprising, in order from 5′ to 3′: (a) a first promoter, (b) a first coding sequence, wherein the first coding sequence encodes anti-EphA2/IL13Ra2 tandem CAR and is operably linked to the first promoter, (c) a second promoter; and (d) a second coding sequence, wherein the second coding sequence encodes a binding triggered transcriptional switch (BTTS) that is activated by binding to EGFRvIII or a brain-specific marker and is operably linked to the second promoter. In these embodiments, transfection of the viral vector into a cytotoxic immune cell results in expression of the BTTS on the surface of the cytotoxic immune cell and binding of the expressed BTTS to an antigen on the surface of a target cell or protein in the extracellular matrix activates expression of the CAR by the cytotoxic immune cell. Methods of treating glioblastoma are also provided.

Dependencies are inferred from the claim text.