Treatment of cancer using a cd123 chimeric antigen receptor

Abstract

The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

What is claimed is: 
     
         1 . A CD123 binding domain comprising a heavy chain variable domain region comprising a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3), and light chain variable domain region comprising a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 3 (LC CDR3), wherein:
 (i) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 487, 492, 497, 502, 507, and 512, respectively; or   (ii) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 517, 522, 527, 532, 537, and 542, respectively.   
     
     
         2 . The CD123 binding domain of  claim 1 , comprising the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 487, 492, 497, 502, 507, and 512, respectively. 
     
     
         3 . The CD123 binding domain of  claim 1 , comprising the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 517, 522, 527, 532, 537, and 542, respectively. 
     
     
         4 . The CD123 binding domain of  claim 1 , comprising:
 (i) the amino acid sequence of the light chain variable region of SEQ ID NO: 276; or   (ii) an amino acid sequence with 95-99% identity to the amino acid sequence of the light chain variable region of SEQ ID NO: 276.   
     
     
         5 . The CD123 binding domain of  claim 1 , comprising:
 (i) the amino acid sequence of the heavy chain variable region of SEQ ID NO: 217; or   (ii) an amino acid sequence with 95-99% identity to the amino acid sequence of the heavy chain variable region of SEQ ID NO: 217.   
     
     
         6 . The CD123 binding domain of  claim 1 , comprising the amino acid sequence of the light chain variable region of SEQ ID NO: 276, and the amino acid sequence of the heavy chain variable region of SEQ ID NO: 217. 
     
     
         7 . The CD123 binding domain of  claim 1 , comprising:
 (i) the amino acid sequence of SEQ ID NO:480;   (ii) an amino acid sequence having at least one, two, or three modifications but not more than 10 modifications to SEQ ID NO: 480; or (iii) an amino acid sequence with 95-99% identity to SEQ ID NO: 480.   
     
     
         8 . The CD123 binding domain of  claim 1 , wherein the CD123 binding domain comprises an antibody fragment. 
     
     
         9 . The CD123 binding domain of  claim 8 , wherein the CD123 binding domain comprises a scFv domain. 
     
     
         10 . The CD123 binding domain of  claim 8 , wherein the CD123 binding domain comprises a Fab domain. 
     
     
         11 . The CD123 binding domain of  claim 1 , wherein the CD123 binding domain is a human binding domain. 
     
     
         12 . The CD123 binding domain of  claim 1 , wherein the CD123 binding domain comprises a linker. 
     
     
         13 . CD123 binding domain of  claim 12 , wherein the linker is present between the VH and VL regions. 
     
     
         14 . The CD123 binding domain of  claim 13 , wherein the scFv comprises the following orientation: light chain variable region—linker—heavy chain variable region. 
     
     
         15 . The CD123 binding domain of  claim 13 , wherein the scFv comprises the following orientation: heavy chain variable region—linker—light chain variable region. 
     
     
         16 . The CD123 binding domain of  claim 12 , wherein the linker comprises the amino acid sequence of any one of SEQ ID NOs: 25-35, 38, 704, or 709. 
     
     
         17 . The CD123 binding domain of  claim 16 , wherein the linker comprises the amino acid sequence of SEQ ID NO: 26.