ADOPTIVE T-CELL THERAPY USING EMPD-SPECIFIC CHIMERIC ANTIGEN RECEPTORS FOR TREATING lgE-MEDIATED ALLERGIC DISEASES

Abstract

A chimeric antigen receptor specific for the extracellular membrane-proximal domain (EMPD) of membrane-bound IgE (mIgE) is provided. The EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon EMPD binding. Nucleic acids and vectors encoding the EMPD-specific chimeric antigen receptor are provided. T cells transduced with such vectors find use in chimeric antigen receptor -based adoptive T-cell therapy for targeting IgE-expressing B cells and treating IgE-mediated allergic diseases.

I claim: 
     
         1 . An EMPD-specific chimeric antigen receptor comprising an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon binding of EMPD to the extracellular ligand binding domain. 
     
     
         2 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the extracellular ligand binding domain comprises a single chain Fv fragment comprising a light chain variable region comprising the complementarity determining regions SEQ ID NO:32, Trp-Ala-Ser and SEQ ID NO:33, and a heavy chain variable region comprising the complementarity determining regions SEQ ID NO: 34, SEQ ID NO:35 and SEQ ID NO:36. 
     
     
         3 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the extracellular ligand binding domain comprises a single chain Fv fragment comprising a light chain variable region comprising the complementarity determining regions SEQ ID NO:37, Trp-Ala-Ser and SEQ ID NO:38, and a heavy chain variable region comprising the complementarity determining regions SEQ ID NO:39, SEQ ID NO:40 and SEQ ID NO:41. 
     
     
         4 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the extracellular ligand binding domain comprises a single chain Fv fragment comprising a light chain variable region comprising the complementarity determining regions SEQ ID NO:42, Leu-Val-Ser and SEQ ID NO:43, and a heavy chain variable region comprising the complementarity determining regions SEQ ID NO:44, SEQ ID NO:45 and SEQ ID NO:46. 
     
     
         5 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the extracellular ligand binding domain comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; 
 (ii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 275 of SEQ ID NO:9. said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or 
 (iii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker. 
 
     
     
         6 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the extracellular ligand binding domain comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said variable light chain and variable heavy chain being connected by a sequence of amino acids forming a flexible linker; 
 (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said variable light chain and variable heavy chain being connected by a sequence of amino acids forming a flexible linker; or 
 (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said variable light chain and variable heavy chain being connected by a sequence of amino acids forming a flexible linker. 
 
     
     
         7 . The EMPD-specific chimeric antigen receptor of  claim 1  which binds to the same EMPD epitope as one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7 
 (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9; or 
 (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31. 
 
     
     
         8 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the intracellular domain comprises an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). 
     
     
         9 . The EMPD-specific chimeric antigen receptor of  claim 8  wherein the intracellular signaling domain comprises a CD3ζ signaling domain. 
     
     
         10 . The EMPD-specific chimeric antigen receptor of  claim 9  wherein the CD3 signaling domain comprises the amino acid sequence SEQ ID NO: 12. 
     
     
         11 . The EMPD-specific chimeric antigen receptor of  claim 8  wherein the intracellular domain comprises a costimulatory signaling domain. 
     
     
         12 . The EMPD-specific chimeric antigen receptor of  claim 11  wherein the costimulatory signaling domain comprises at least the intracellular domain of at least one of 4-1BB, CD27, CD28, CD134 or ICOS. 
     
     
         13 . The EMPD-specific chimeric antigen receptor of  claim 12  wherein the costimulatory signaling domain comprises at least the intracellular domain of CD28 or 4-1BB, or at least the intracellular domains of both CD28 and 4-1BB. 
     
     
         14 . The EMPD-specific chimeric antigen receptor of  claim 12  wherein the costimulatory signaling domain comprises the amino acid sequence SEQ ID NO:48. 
     
     
         15 . The EMPD-specific chimeric antigen receptor of  claim 1  wherein the transmembrane domain comprises the amino acid sequence SEQ ID NO:22. 
     
     
         16 . The EMPD-specific chimeric antigen receptor of  claim 8  comprising an amino acid sequence selected from the group of amino sequences consisting of the following:
 (a) SEQ ID NO:7; 
 (b) the sequence of amino acids from amino acid 23 to amino acid 559 of SEQ ID NO:7; 
 (c) SEQ ID NO:9; 
 (d) the sequence of amino acids from amino acid 23 to amino acid 554 of SEQ ID NO:9; 
 (e) SEQ ID NO:31; and 
 (f) the sequence of amino acids from amino acid 23 to amino acid 552 of SEQ ID NO:31. 
 
     
     
         17 . An isolated nucleic acid sequence encoding an EMPD-specific chimeric antigen receptor wherein the an EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon binding of EMPD to the extracellular ligand binding domain. 
     
     
         18 . The isolated nucleic acid sequence according to  claim 17 , wherein the encoded extracellular ligand binding domain comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         19 . The isolated nucleic acid sequence according to  claim 17 , wherein the encoded extracellular ligand binding domain comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         20 . The isolated nucleic acid sequence according to  claim 17 , wherein the encoded EMPD-specific chimeric antigen receptor binds to the same EMPD epitope as one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         21 . The isolated nucleic acid sequence according to  claim 17 , wherein the encoded intracellular domain comprises an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). 
     
     
         22 . The isolated nucleic acid sequence according to  claim 21 , wherein the encoded intracellular signaling domain comprises a CD3 signaling domain. 
     
     
         23 . The isolated nucleic acid sequence according to  claim 22 , wherein the encoded CD3ζ signaling domain comprises the amino acid sequence SEQ ID NO: 12. 
     
     
         24 . The isolated nucleic acid sequence according to  claim 21 , wherein the encoded intracellular domain comprises a costimulatory signaling domain. 
     
     
         25 . The isolated nucleic acid sequence according to  claim 24 , wherein the encoded costimulatory signaling domain comprises at least the intracellular domain of at least one of 4-1BB, CD27, CD28, CD134 or ICOS. 
     
     
         26 . The isolated nucleic acid sequence according to  claim 25 , wherein the encoded costimulatory signaling domain comprises at least the intracellular domain of CD28 or 4-1BB, or at least the intracellular domains of both CD28 and 4-1BB. 
     
     
         27 . The isolated nucleic acid sequence according to  claim 25 , wherein the encoded costimulatory signaling domain comprises the amino acid sequence SEQ ID NO:48. 
     
     
         28 . The isolated nucleic acid sequence according to  claim 21 , wherein the nucleic acid sequence encodes an EMPD-specific chimeric antigen receptor having an amino acid sequence selected from the group of amino sequences consisting of the following:
 (a) SEQ ID NO:7;   (b) the sequence of amino acids from amino acid 23 to amino acid 559 of SEQ ID NO:7;   (c) SEQ ID NO:9;   (d) the sequence of amino acids from amino acid 23 to amino acid 554 of SEQ ID NO:9;   (e) SEQ ID NO:31; and   (f) the sequence of amino acids from amino acid 23 to amino acid 552 of SEQ ID NO:31.   
     
     
         29 . The isolated nucleic acid sequence according to  claim 28 , comprising a nucleic acid sequence selected from the group consisting of:
 (a) SEQ ID NO:6;   (b) the sequence of nucleotides from nucleotide 67 to nucleotide 1677 of SEQ ID NO:6;   (c) SEQ ID NO:8;   (d) the sequence of nucleotides from nucleotide 67 to nucleotide 1662 of SEQ ID NO:8;   (e) SEQ ID NO:30; and   (f) the sequence of nucleotides from nucleotide 67 to nucleotide 1656 of SEQ ID NO: 30.   
     
     
         30 . A T cell comprising a nucleic acid sequence encoding an EMPD-specific chimeric antigen receptor, wherein the EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon binding of EMPD to the extracellular ligand binding domain. 
     
     
         31 . A T cell expressing an EMPD-specific chimeric antigen receptor, wherein the EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon binding of EMPD to the extracellular ligand binding domain. 
     
     
         32 . The T cell according to  claim 31 , wherein the extracellular ligand binding domain of the EMPD-specific chimeric antigen receptor comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising complementarity determining regions SEQ ID NO:32, Trp-Ala-Ser and SEQ ID NO:33, and a heavy chain variable region comprising the complementarity determining regions SEQ ID NO:34, SEQ ID NO:35 and SEQ ID NO:36, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising complementarity determining regions SEQ ID NO:37, Trp-Ala-Ser and SEQ ID NO:38, and a heavy chain variable region comprising the complementarity determining regions SEQ ID NO:39, SEQ ID NO:40 and SEQ ID NO:41, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region comprising complementarity determining regions SEQ ID NO:42, Leu-Val-Ser and SEQ ID NO:43, and a heavy chain variable region comprising the complementarity determining regions SEQ ID NO:44, SEQ ID NO:45 and SEQ ID NO:46, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         33 . The T cell according to  claim 31 , wherein the extracellular ligand binding domain of the EMPD-specific chimeric antigen receptor comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         34 . The T cell according to  claim 31 , wherein the extracellular ligand binding domain of the EMPD-specific chimeric antigen receptor comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         35 . The T cell according to  claim 31 , wherein the extracellular ligand binding domain of the EMPD-specific chimeric antigen receptor comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         36 . The T cell according to  claim 31 , wherein the intracellular domain comprises an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). 
     
     
         37 . The T cell according to  claim 36 , wherein the intracellular signaling domain comprises a CD3ζ signaling domain. 
     
     
         38 . The T cell according to  claim 37 , wherein the CD3 signaling domain comprises the amino acid sequence SEQ ID NO: 12. 
     
     
         39 . The T cell according to  claim 36 , wherein the EMPD-specific chimeric antigen receptor further comprises a costimulatory signaling domain. 
     
     
         40 . The T cell according to  claim 39  wherein the costimulatory signaling domain comprises at least the intracellular domain of at least one of 4-1BB, CD27, CD28, CD134 or ICOS. 
     
     
         41 . The T cell according to  claim 40  wherein the costimulatory signaling domain comprises at least the intracellular domain of CD28 or 4-1BB, or at least the intracellular domains of both CD28 and 4-1BB. 
     
     
         42 . The T cell according to  claim 40  wherein the costimulatory signaling domain comprises the amino acid sequence SEQ ID NO: 48. 
     
     
         43 . The T cell according to  claim 31 , wherein the transmembrane domain has the amino acid sequence SEQ ID NO: 12. 
     
     
         44 . The T cell according to  claim 36 , wherein the EMPD-specific chimeric antigen receptor comprises an amino acid sequence selected from the group of amino sequences consisting of the following:
 (a) SEQ ID NO:7;   (b) the sequence of amino acids from amino acid 23 to amino acid 559 of SEQ ID NO:7;   (c) SEQ ID NO:9;   (d) the sequence of amino acids from amino acid 23 to amino acid 554 of SEQ ID NO:9;   (e) SEQ ID NO:31; and   (f) the sequence of amino acids from amino acid 23 to amino acid 552 of SEQ ID NO:31.   
     
     
         45 . A vector comprising a nucleic acid sequence encoding an EMPD-specific chimeric antigen receptor wherein the an EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon binding of EMPD to the extracellular ligand binding domain. 
     
     
         46 . The vector according to  claim 45 , wherein the encoded extracellular ligand binding domain comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region having at least 95% sequence identity with the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region having at least 95% sequence identity with the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         47 . The vector according to  claim 45 , wherein the encoded extracellular ligand binding domain comprises one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         48 . The vector according to  claim 45 , wherein the encoded EMPD-specific chimeric antigen receptor binds to the same EMPD epitope as one of the following single chain Fv fragments:
 (i) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:7 and a heavy chain variable region comprising the sequence of amino acids 152 to 275 of SEQ ID NO:7, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker;   (ii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 136 of SEQ ID NO:9 and a heavy chain variable region comprising the sequence of amino acids 152 to 270 of SEQ ID NO:9, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker; or   (iii) a single chain Fv fragment comprising a light chain variable region comprising the sequence of amino acids 23 to 135 of SEQ ID NO:31 and a heavy chain variable region comprising the sequence of amino acids 151 to 268 of SEQ ID NO:31, said light chain variable region and heavy chain variable region being connected by a sequence of amino acids forming a flexible linker.   
     
     
         49 . The vector according to  claim 45 , wherein the encoded intracellular domain comprises an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). 
     
     
         50 . The vector according to  claim 46 , wherein the encoded intracellular signaling domain comprises a CD3ζ signaling domain. 
     
     
         51 . The vector according to  claim 49 , wherein the encoded intracellular domain comprises a costimulatory signaling domain. 
     
     
         52 . The vector according to  claim 51 , wherein the encoded costimulatory signaling domain comprises at least the intracellular domain of at least one of 4-1BB, CD27, CD28, CD134 or ICOS. 
     
     
         53 . The vector according to  claim 52 , wherein the encoded costimulatory signaling domain comprises at least the intracellular domain of CD28 or 4-1BB, or at least the intracellular domains of both CD28 and 4-1BB. 
     
     
         54 . The vector according to  claim 52 , wherein the encoded costimulatory signaling domain comprises the amino acid sequence SEQ ID NO: 48. 
     
     
         55 . The vector according to  claim 49 , wherein the nucleic acid sequence encodes an EMPD-specific chimeric antigen receptor comprising an amino acid sequence selected from the group of amino sequences consisting of the following:
 (a) SEQ ID NO: 7;   (b) the sequence of amino acids from amino acid 23 to amino acid 559 of SEQ ID NO:7;   (c) SEQ ID NO: 9;   (d) the sequence of amino acids from amino acid 23 to amino acid 554 of SEQ ID NO:9;   (e) SEQ ID NO:31; and   (f) the sequence of amino acids from amino acid 23 to amino acid 552 of SEQ ID NO:31.   
     
     
         56 . The vector according to  claim 55 , comprising a nucleic acid sequence selected from the group consisting of:
 (a) SEQ ID NO:6;   (b) the sequence of nucleotides from nucleotide 67 to nucleotide 1677 of SEQ ID NO:6;   (c) SEQ ID NO:8;   (d) the sequence of nucleotides from nucleotide 67 to nucleotide 1662 of SEQ ID NO:8;   (e) SEQ ID NO:30; and   (f) the sequence of nucleotides from nucleotide 67 to nucleotide 1656 of SEQ ID NO: 30.   
     
     
         57 . A method for stimulating a T cell-mediated immune response to cells expressing mIgE in a subject, the method comprising administering to the subject an effective amount of T cells according to  claim 31 . 
     
     
         58 . The method according to  claim 57  wherein the T cells comprise autologous T cells that are removed from the subject and engineered ex vivo to express said CAR and administered to the subject. 
     
     
         59 . A method for treating an IgE-mediated allergic disease in a subject in need of such treatment, or for preventing an IgE-mediated allergic disease in a subject at risk of such disease, comprising administering to the subject an effective amount of T cells according to  claim 31 . 
     
     
         60 . The method according to  claim 59  wherein the T cells comprise autologous T cells that are removed from the subject and engineered ex vivo to express said CAR and administered to the subject. 
     
     
         61 . The method according to  claim 59  wherein the disease is selected from the group consisting of allergic asthma, food allergy, atopic dermatitis, allergic rhinitis, allergic rhinoconjunctivitis, chronic urticaria and systematic anaphylaxis.