Chimeric antigen receptor

Abstract

The present invention provides a chimeric antigen recept- or (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

1 - 18 . (canceled) 
     
     
         19 . A nucleic acid encoding a chimeric antigen receptor (CAR) which comprises:
 (i) truncated proliferation-inducing ligand (APRIL) that
 (a) binds B cell maturation antigen (BCMA) and 
 (b) binds transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI); 
   (ii) a spacer domain; and   (ii) a transmembrane domain; and   (iii) an intracellular T cell signaling domain.   
     
     
         20 . The nucleic acid according to  claim 19 , wherein the truncated APRIL lacks the amino terminal portion of APRIL responsible for proteoglycan binding. 
     
     
         21 . The nucleic acid according to  claim 20 , which comprises the sequence shown as SEQ ID NO: 14. 
     
     
         22 . The nucleic acid according to  claim 19 , wherein the transmembrane and intracellular T-cell signalling domain comprise the sequence shown as SEQ ID NO: 7. 
     
     
         23 . The nucleic acid according to  claim 19 , wherein the spacer comprises one of the following: a human IgG1 spacer, an IgG1 hinge, or a CD8 stalk. 
     
     
         24 . The nucleic acid according to  claim 23 , wherein the spacer comprises a CD8 stalk. 
     
     
         25 . The nucleic acid according to  claim 19  which encodes the sequence shown as SEQ ID NO: 1, 2, 3, 4, 5 or 6. 
     
     
         26 . A nucleic acid sequence according to  claim 19  which comprises the sequence shown as SEQ ID NO: 15, 16, 17, 18, 19 or 20. 
     
     
         27 . A vector which comprises a nucleic acid sequence according to  claim 19 . 
     
     
         28 . A T cell or NK cell which expresses a CAR according to  claim 19 . 
     
     
         29 . A method for making a T cell or NK cell, which comprises the step of introducing a nucleic acid according to  claim 19  into a T cell or NK cell. 
     
     
         30 . A pharmaceutical composition which comprises a vector according to  claim 27  together with a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         31 . A pharmaceutical composition which comprises a cell according to  claim 28  together with a pharmaceutically acceptable carrier, diluent or excipient.