Chimeric antigen receptors targeting cd-19

Abstract

The invention is directed to a chimeric antigen receptor (CAR) directed against CD19, which comprises an amino acid sequence of any one of SEQ ID NO: 1-SEQ ID NO: 13. The invention also provides T-cells expressing the CAR and methods for destroying malignant B-cells.

1 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) directed against CD19, wherein the CAR comprises an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13. 
     
     
         2 . The population of cells of  claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 10. 
     
     
         3 . The population of cells of  claim 1 , wherein the host cell is a T-cell. 
     
     
         4 . The population of cells of  claim 1 , wherein the host cell is an NK cell. 
     
     
         5 . The population of cells of  claim 2 , wherein the host cell is a T-cell. 
     
     
         6 . The population of cells of  claim 2 , wherein the host cell is an NK cell. 
     
     
         7 . A pharmaceutical composition comprising the population of cells of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         8 . A pharmaceutical composition comprising the population of cells of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         9 . A pharmaceutical composition comprising the population of cells of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         10 . A pharmaceutical composition comprising the population of cells of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         11 . A pharmaceutical composition comprising the population of cells of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         12 . A pharmaceutical composition comprising the population of cells of  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         13 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence of each of the following that are present in SEQ ID NO: 4 or SEQ ID NO: 9:
 (i) the extracellular spacer,   (ii) the transmembrane domain derived from a human CD8α molecule, and   (iii) the intracellular T-cell signaling domains derived from
 (a) one or both of a human CD28 molecule and a human CD27 molecule, and 
 (b) a human CD3ζ molecule. 
   
     
     
         14 . The population of cells of  claim 13 , wherein the host cell is a T-cell or an NK cell. 
     
     
         15 . A pharmaceutical composition comprising the population of cells of  claim 14  and a pharmaceutically acceptable carrier. 
     
     
         16 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence of each of the following that are present in SEQ ID NO: 10 or SEQ ID NO: 11:
 (i) the extracellular spacer,   (ii) the transmembrane domain derived from a human CD8α molecule, and   (iii) the intracellular T-cell signaling domains derived from
 (a) one or both of a human CD28 molecule and a human CD27 molecule, and 
 (b) the gamma chain of FcεRI. 
   
     
     
         17 . The population of cells of  claim 16 , wherein the host cell is a T-cell or an NK cell. 
     
     
         18 . A pharmaceutical composition comprising the population of cells of  claim 17  and a pharmaceutically acceptable carrier. 
     
     
         19 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence of each of the following that are present in SEQ ID NO: 12 or SEQ ID NO: 13:
 (i) the extracellular spacer,   (ii) the transmembrane domain derived from a human CD8α molecule, and   (iii) the intracellular T-cell signaling domains derived from a human CD28 molecule and the gamma chain of FcεRI.   
     
     
         20 . The population of cells of  claim 19 , wherein the host cell is a T-cell or an NK cell. 
     
     
         21 . A pharmaceutical composition comprising the population of cells of  claim 20  and a pharmaceutically acceptable carrier.