Methods and compositions for eliminating engineered immune cells

An in-vitro method for generating engineered immune cells, the method comprising modifying immune cells by introduction into said immune cells

• a) an inducible gene expression system comprising
• I) a first nucleic acid comprising a drug-inducible promoter operably linked to a second nucleic acid
• II) said second nucleic acid encoding a polypeptide or ncRNA which decreases cell surface expression level of major histocompatibility complex (MHC) class I relative to cell surface expression level of MHC class I of an immune cell that does not express the polypeptide or ncRNA
• b) a third nucleic acid encoding a chimeric antigen receptor (CAR) or TCR,
• wherein when a drug that induces said drug-inducible promoter is administered to said immune cells, the gene expression system is induced and said polypeptide or ncRNA is expressed.

A combination of pharmaceutical compositions comprising

• A) a composition of immune cells comprising
• a) an inducible gene expression system comprising
• I) a first nucleic acid comprising a drug-inducible promoter operably linked to a second nucleic acid
• II) said second nucleic acid encoding a polypeptide or ncRNA which decreases cell surface expression level of major histocompatibility complex (MHC) class I relative to cell surface expression level of MHC class I of an immune cell that does not express the polypeptide or ncRNA
• b) a third nucleic acid encoding a chimeric antigen receptor (CAR) or TCR,
• and optional a pharmaceutical acceptable carrier, and
• B) a composition of a drug that induces said drug-inducible promoter,
• and optional pharmaceutical acceptable carrier.