Anti-b-cell maturation antigen chimeric antigen receptors with human domains

Abstract

Provided are chimeric antigen receptors (CARs) having antigen specificity for B-cell Maturation Antigen (BCMA). Also provided are related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs. Methods of treating or preventing cancer in a mammal are also provided.

1 . A chimeric antigen receptor (CAR) comprising an antigen recognition domain, a transmembrane (TM) domain, and a T cell activation domain, wherein the CAR has antigen specificity for B-cell maturation antigen (BCMA), wherein the antigen recognition domain comprises the amino acid sequences of:
 (a) SEQ ID NOs: 1-3;   (b) SEQ ID NOs: 4-6;   (c) SEQ ID NOs: 7-9; or   (d) SEQ ID NOs: 10-12.   
     
     
         2 . The CAR of  claim 1 , wherein all domains of the CAR are human. 
     
     
         3 . The CAR of  claim 1 , wherein the antigen recognition domain does not comprise a linker peptide having a length of about 8 to about 40 amino acid residues. 
     
     
         4 . The CAR of  claim 1 , wherein the CAR does not comprise an antibody light chain variable region. 
     
     
         5 . The CAR of  claim 1 , wherein the antigen recognition domain comprises the amino acid sequence of:
 (a) SEQ ID NO: 13;   (b) SEQ ID NO: 14;   (c) SEQ ID NO: 15; or   (d) SEQ ID NO: 16.   
     
     
         6 . The CAR of  claim 1 , wherein the T-cell activation domain comprises a T-cell signaling domain of any one of the following proteins: a human CD28 protein, a human CD3-zeta protein, a human FcRγ protein, a CD27 protein, an OX40 protein, a human 4-1BB protein, a human inducible T-cell costimulatory protein (ICOS), modified versions of any of the foregoing, or any combination of the foregoing. 
     
     
         7 . The CAR of  claim 1  comprising the amino acid sequence of any one of SEQ ID NOs: 17-28. 
     
     
         8 . A nucleic acid comprising a nucleotide sequence encoding the CAR of  claim 1 . 
     
     
         9 . The nucleic acid of  claim 8  comprising the nucleotide sequence of any one of SEQ ID NOs: 29-40. 
     
     
         10 . A vector comprising the nucleic acid of  claim 8 . 
     
     
         11 . An isolated host cell comprising the vector of  claim 10 . 
     
     
         12 . The isolated host cell of  claim 11 , wherein the host cell is a T-cell. 
     
     
         13 . The isolated host cell of  claim 11 , wherein the host cell is a natural killer (NK) cell. 
     
     
         14 . A population of cells comprising at least one host cell of  claim 11 . 
     
     
         15 .- 16 . (canceled) 
     
     
         17 . A method of treating or preventing cancer in a mammal, the method comprising administering to the mammal the CAR of  claim 1  in an amount effective to treat or prevent cancer in the mammal. 
     
     
         18 . The method of  claim 17 , wherein the cancer is multiple myeloma or Hodgkin's lymphoma. 
     
     
         19 . A pharmaceutical composition comprising the CAR of  claim 1  and a pharmaceutically acceptable carrier.