Methods of treating glioblastomas

Abstract

Provided herein is a method of treating a subject for a glioblastoma, the method comprising: administering to the subject an immune cell genetically modified with: (a) a nucleic acid sequence encoding a binding triggered transcriptional switch (BTTS) that binds to a priming antigen that is tissue-specifically expressed in the central nervous system; (b) a nucleic acid sequence encoding a tandem chimeric antigen receptor (CAR) or T cell receptor (TCR) that has a first binding domain that recognizes Ephrin type-A receptor 2 (EphA2) and a second binding domain that recognizes Interleukin-13 receptor subunit alpha-2 (IL13RA2); and (c) a regulatory sequence operably linked to (b) that is responsive to the BTTS, wherein binding of the BTTS to the priming antigen activates expression of the tandem CAR or TCR, which binds EphA2 and/or IL13RA2 in the glioblastoma and induces killing of glioblastoma cells.

Dependencies are inferred from the claim text.