Systems and methods for targeting cancer cells
The present disclosure provides immune cells genetically modified to produce two antigentriggered polypeptides, each recognizing a different cell surface antigen, wherein the two different cell surface antigens employed are selected from those pairs described herein. The present disclosure further provides systems comprising two antigen-triggered polypeptides (or nucleic acids encoding same), each recognizing a different cell surface antigen, wherein the two different cell surface antigens employed are selected from those pairs described herein. Also provided are method of killing a target cancer cell, using the described genetically modified immune cells and/or systems. The present disclosure also provides poly specific-immune inducing polypeptides including first and second antigen binding domains specific for first and second antigens, respectively, present on the surface of a target cancer cell.
1 . An in vitro or ex vivo genetically modified cytotoxic immune cell, wherein the cytotoxic immune cell is genetically modified to produce: (a) a binding triggered transcriptional switch (BTTS) that recognizes PTPRZ1, and (b) an antigen-specific therapeutic that recognizes IL13RA2, wherein binding of the BTTS to PTPRZ1 induces expression of the antigen-specific therapeutic by the cell.
2 . The cell of claim 1 , wherein: the antigen-specific therapeutic is a chimeric antigen receptor (CAR) that recognizes IL13RA2, wherein binding of the BTTS to PTPRZ1 induces expression of the CAR by the cell.
3 . The cell of claim 2 , wherein the BTTS comprises:
an extracellular domain that comprises binding domains that bind to PTPRZ1;
a transmembrane domain,
one or more protease cleavage domains; and
a transcriptional activator,
wherein binding of the extracellular domain to PTPRZ1 results in cleavage of the BTTS at the one or more protease cleavage domains to release the transcriptional activator, and wherein the released transcriptional activator activates expression of the CAR.