CAR T-CELLS RECOGNIZING CANCER-SPECIFIC IL 13Ra2

Abstract

Provided are specific binding molecules, or fragments thereof, that bind to an epitope of IL13Rα2, a receptor polypeptide preferentially found on the surface of cancer cells rather than healthy cells. Exemplary specific binding molecules are bispecific binding molecules that comprise a fragment of an IL13Rα2 binding molecule and a peptide providing a second function providing a signaling function of the signaling domain of a T cell signaling protein, a peptide modulator of T cell activation, or an enzymatic component of a labeling system. Also provided are polynucleotides encoding such a specific binding molecule (e.g., bispecific binding molecule), vectors, host cells, pharmaceutical compositions and methods of preventing, treating or ameliorating a symptom associated with a cancer disease such as a solid tumor disease (e.g., glioblastoma multiforme).

1 - 31 . (canceled) 
     
     
         32 . An IL13Rα2-specific chimeric antigen receptor (CAR) comprising:
 (A) an ectodomain comprising each of the amino acid sequences of: 
 
       
         
           
                 
                 
               
                     
                   (i) 
                 
                     
                   (SEQ ID NO: 1) 
                 
                     
                   NYLMN; 
                 
                     
                     
                 
                     
                   (ii) 
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   RIDPYDGDIDYNQNFKD; 
                 
                     
                     
                 
                     
                   (III) 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   GYGTAYGVDY; 
                 
                     
                     
                 
                     
                   (iv) 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   RASESVDNYGISFMN; 
                 
                     
                     
                 
                     
                   (v) 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   AASRQGSG; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (vi) 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   QQSKEVPWT; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (B) a spacer region; 
         (C) a transmembrane domain; and 
         (D) an endodomain selected from the group consisting of CD3.ζ, CD28.ζ, CD28.OX40.ζ, CD28.41BB.ζ and 41BB.ζ. 
       
     
     
         33 - 35 . (canceled) 
     
     
         36 . The IL13Rα2-specific CAR of  claim 32  wherein the spacer region comprises SEQ ID NO:103, SEO ID NO:35, or SEO ID NO:37. 
     
     
         37 . The IL13Rα2-specific CAR of  claim 32  wherein the transmembrane domain is the transmembrane domain of CD28 or CD8α. 
     
     
         38 . The IL13Rα2-specific CAR of  claim 37 , wherein the transmembrane domain of CD28 comprises the amino acid sequence of SEQ ID NO: 39. 
     
     
         39 . The IL13Rα2-specific CAR of  claim 32 , wherein the endodomain comprises a signaling domain of one or more of: CD137, CD134, CD27, CD40, ICOS, or Myd88. 
     
     
         40 - 41 . (canceled) 
     
     
         42 . The IL13Rα2-specific CAR of  claim 32 , comprising the amino acid sequence of SEQ ID NO: 47. 
     
     
         43 - 47 . (canceled) 
     
     
         48 . The IL13Rα2-specific CAR of  claim 32 , comprising the amino acid sequence of SEQ ID NO: 53 or SEQ ID NO: 55. 
     
     
         49 . A nucleic acid encoding the IL13Rα2-specific CAR of  claim 32 . 
     
     
         50 . (canceled) 
     
     
         51 . A vector comprising the nucleic acid of  claim 49 . 
     
     
         52 . (canceled) 
     
     
         53 . A host cell comprising the vector of  claim 51 . 
     
     
         54 . The host cell of  claim 53 , which is a human host cell. 
     
     
         55 . The host cell of  claim 53 , which is a T-lymphocyte or a natural killer cell. 
     
     
         56 - 59 . (canceled) 
     
     
         60 . A pharmaceutical composition comprising the IL13Rα2-specific CAR of  claim 32 . 
     
     
         61 . A method of treating a cancer in a subject, comprising administering to the subject a population of cells comprising the IL13Rα2-specific CAR of  claim 32 , in an amount effective to treat the cancer in the subject. 
     
     
         62 - 63 . (canceled) 
     
     
         64 . The method of  claim 61 , wherein the population of cells are T-lymphocytes or natural killer cells. 
     
     
         65 . (canceled) 
     
     
         66 . An IL13Rα2 binding agent comprising each of the amino acid sequences of: (a) complementarity determining region 1 (NYLMN (SEQ ID NO: 1)); (b) complementarity determining region 2 (RIDPYDGDIDYNQNFKD (SEQ ID NO: 2)); (c) complementarity determining region 3 (GYGTAYGVDY (SEQ ID NO: 3)); (d) complementarity determining region 4 (RASESVDNYGISFMN (SEQ ID NO: 4)); (e) complementarity determining region 5 (AASRQGSG (SEQ ID NO: 5)); and (f) complementarity determining region 6 (QQSKEVPWT (SEQ ID NO: 6)). 
     
     
         67 . The IL13Rα2 binding agent of  claim 66 , comprising one or both of the amino acid sequences of SEQ ID NO: 7 and/or SEQ ID NO: 8. 
     
     
         68 . The IL13Rα2 binding agent of  claim 66 , wherein the agent comprises a polypeptide of SEQ ID NO: 13. 
     
     
         69 . A nucleic acid encoding the IL13Rα2 binding agent of  claim 66 . 
     
     
         70 . A method of treating glioblastoma multiforme or colon cancer in a subject, comprising administering to the subject a binding agent of  claim 66 , in an amount effective to treat the cancer in the subject.