T cell receptors directed against bob1 and uses thereof

Abstract

The technology relates in part to compositions and methods for inducing an immune response against a Bob1 antigen. Provided are methods for treating hyperproliferative diseases by inducing an immune response against a Bob1 antigen; the immune response may be induced using a Bob1 polypeptide fragment, or by specifically targeting Bob1-expressing cells using T cell receptors directed against Bob1.

1 .- 11 . (canceled) 
     
     
         12 . A method of enhancing an immune response in a subject diagnosed with a hyperproliferative disease or condition, comprising administering a therapeutically effective amount of a modified cell to the subject:
 wherein the modified cell is transfected or transduced with a nucleic acid molecule;   wherein the nucleic acid molecule comprises a promoter operatively linked to a polynucleotide that encodes a complementarity determining region 3 (CDR3) region of a T cell receptor that specifically binds to Bob1, wherein the polynucleotide comprises:   a) a first nucleotide sequence that encodes a first polypeptide comprising a CDR3 region of a TCRα polypeptide; and   b) a second nucleotide sequence that encodes a second polypeptide comprising a CDR3 region of a TCRβ polypeptide,   wherein the CDR3 regions of the TCRα polypeptide and TCRβ polypeptide together specifically bind to Bob1.   
     
     
         13 . A method for stimulating a cell mediated immune response to a target cell population or tissue in a subject, comprising administering a modified cell to the subject:
 wherein the modified cell is transfected or transduced with a nucleic acid molecule;   wherein the nucleic acid molecule comprises a promoter operatively linked to a polynucleotide that encodes a complementarity determining region 3 (CDR3) region of a T cell receptor that specifically binds to Bob1, wherein the polynucleotide comprises:   a) a first nucleotide sequence that encodes a first polypeptide comprising a CDR3 region of a TCRα polypeptide; and   b) a second nucleotide sequence that encodes a second polypeptide comprising a CDR3 region of a TCRβ polypeptide,   wherein the CDR3 regions of the TCRα polypeptide and TCRβ polypeptide together specifically bind to Bob1.   
     
     
         14 . The method of  claim 13 , wherein the number or concentration of target cells in the subject is reduced following administration of the modified cell. 
     
     
         15 . The method of  claim 13 , wherein the modified cell further comprises a second nucleic acid molecule comprising a third nucleotide sequence encoding a chimeric Caspase-9 polypeptide, wherein the chimeric Caspase-9 polypeptide comprises a multimeric ligand binding region and a Caspase-9 polypeptide. 
     
     
         16 . The method of  claim 15 , wherein the method further comprises administering a multimeric ligand that binds to the multimeric ligand binding region to the subject following administration of the modified cell to the subject. 
     
     
         17 . The method of  claim 16 , wherein after administration of the multimeric ligand, the number or concentration of modified cell comprising the chimeric Caspase-9 polypeptide is reduced in a sample obtained from the subject after administering the multimeric ligand compared to the number or concentration of modified cell comprising the chimeric Caspase-9 polypeptide in a sample obtained from the subject before administering the multimeric ligand. 
     
     
         18 - 25 . (canceled) 
     
     
         26 . The method of  claim 12 , wherein the CDR3 region of the TCRα polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 25, and the CDR3 region of the TCRβ polypeptide comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 28. 
     
     
         27 . The method of  claim 13 , wherein the CDR3 region of the TCRα polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 25, and the CDR3 region of TCRβ polypeptide comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 28. 
     
     
         28 . The method of  claim 15 , wherein the CDR3 region of the TCRα polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 25, and the CDR3 region of the TCRβ polypeptide comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 28. 
     
     
         29 . The method of  claim 12 , wherein the CDR3 region of the T cell receptor specifically binds to a Bob1 polypeptide comprising the amino acid sequence of APAPTAVVL (SEQ ID NO: 118) or the amino acid sequence YALNHTLSV (SEQ ID NO: 119). 
     
     
         30 . The method of  claim 13 , wherein the CDR3 region of the T cell receptor specifically binds to a Bob1 polypeptide comprising the amino acid sequence of APAPTAVVL (SEQ ID NO: 118) or the amino acid sequence YALNHTLSV (SEQ ID NO: 119). 
     
     
         31 . The method of  claim 15 , wherein the CDR3 region of the T cell receptor specifically binds to a Bob1 polypeptide comprising the amino acid sequence of APAPTAVVL (SEQ ID NO: 118) or the amino acid sequence YALNHTLSV (SEQ ID NO: 119). 
     
     
         32 . The method of  claim 12 , wherein
 a) the first nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 2 or SEQ ID NO: 3, and the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 6; or   b) the first nucleotide comprises the nucleotide sequence of SEQ ID NO: 26 or SEQ ID NO: 27, and the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 29 or SEQ ID NO: 30.   
     
     
         33 . The method of  claim 13 , wherein
 a) the first nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 2 or SEQ ID NO: 3, and the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 6; or   b) the first nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 26 or SEQ ID NO: 27, and the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 29 or SEQ ID NO: 30.   
     
     
         34 . The method of  claim 15 , wherein
 a) the first nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 2 or SEQ ID NO: 3, and the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 6; or   b) the first nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 26 or SEQ ID NO: 27, and the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO:   29 or SEQ ID NO: 30.   
     
     
         35 . The method of  claim 15 , wherein the multimeric binding region is a FKBP ligand binding region.