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, CD28.41 BB.ζ and 41BB.ζ. 
       
     
     
         33 .- 35 . (canceled) 
     
     
         36 . The IL13Rα2-specific chimeric antigen receptor of  claim 32  wherein the spacer region comprises SEQ ID NO:103, SEQ ID NO:35, or SEQ ID NO:37. 
     
     
         37 . The IL13Rα2-specific chimeric antigen receptor 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 . (canceled) 
     
     
         41 . The IL13Rα2-specific CAR of  claim 32 , wherein the CD3 zeta chain signaling domain comprises the amino acid sequence of SEQ ID NO: 41. 
     
     
         42 . The IL13Rα2-specific CAR of  claim 32 , comprising the amino acid sequence of SEQ ID NO: 47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, or at least one of SEQ ID NO:7 and SEQ ID NO:8. 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . The IL13Rα2-specific CAR of  claim 42 , wherein the amino acid sequence of SEQ ID NO: 7 is fused to the amino acid sequence of SEQ ID NO: 8 through a linker. 
     
     
         46 . The IL13Rα2-specific CAR of  claim 45 , wherein the linker comprises the amino acid sequence of EEGEFSEAR (SEQ ID NO 10). 
     
     
         47 . The IL13Rα2-specific CAR of  claim 46 , comprising the amino acid sequence of SEQ ID NO: 13. 
     
     
         48 . (canceled) 
     
     
         49 . A nucleic acid encoding the IL13Rα2-specific CAR of  claim 32 . 
     
     
         50 . The nucleic acid of  claim 49 , comprising the sequence of SEQ ID NO: 34, 36, 38, 40, 42, 44, 46, 48, 50, 54, 56, or 65. 
     
     
         51 . The nucleic acid of  claim 49 , wherein the nucleic acid is localized in a vector. 
     
     
         52 . (canceled) 
     
     
         53 . The vector of  claim 51 , wherein the vector is localized in a host cell. 
     
     
         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 . The IL13Rα2-specific CAR of  claim 32  wherein the CAR is combined with a pharmaceutically acceptable carrier in a pharmaceutical composition. 
     
     
         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 . The method of  claim 61 , wherein the cancer is gliobastoma multiforme or colon cancer. 
     
     
         63 . The method of  claim 61 , wherein the population of cells is obtained from the subject. 
     
     
         64 . The method of  claim 63 , wherein the cells are T-lymphocytes or natural killer cells obtained from the subject. 
     
     
         65 . (canceled) 
     
     
         66 . The nucleic acid of  claim 47 , wherein the nucleic acid is combined with a pharmaceutically acceptable carrier in a pharmaceutical composition.