T cell receptor and uses thereof
AssigneeMedical & Biological Laboratories Co., Ltd.
InventorsKazue Watanabe, Shingo Toji
Life of this patent
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Abstract
A method has been developed to efficiently proliferate and culture a CTL specific to WT1 peptides under limiting dilution conditions. Utilizing this method, CTLs capable of recognizing both a state where a wildtype WT1 specific peptide is presented by HLA-A*24:02 and a state where a mutant WT1 specific peptide is presented by HLA-A*24:02 have been successfully obtained.
Claims18
A nucleic acid comprising:
- (1) a cDNA sequence encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- and (2) a cDNA sequence encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7.
A cDNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7.
A vector comprising (a) or (b) below:
- (a) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- or
- (b) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7.
A transformed cell comprising (a) or (b) below:
- (a) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- or
- (b) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7.
A transformed cell comprising a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3 and a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7, the transformed cell being detectable by a molecule multimerized by binding a wildtype WT1 peptide restricted to HLA-A*24:02 and a molecule multimerized by binding a mutant WT1 peptide restricted to HLA-A*24:02.
A kit for detecting any one of a wildtype WT1 peptide restricted to HLA-A*24:02 and a mutant WT1 peptide restricted to HLA-A*24:02, the kit comprising at least one of (d) to (f) below and instructions for using the kit:
- (d) a cDNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3, and a cDNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- (e) a vector comprising a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- or
- (f) a transformed cell comprising a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- or
- (f)(2) a transformed cell comprising a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3 and a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7, the transformed cell being detectable by a molecule multimerized by binding a wildtype WT1 peptide restricted to HLA-A*24:02 and a molecule multimerized by binding a mutant WT1 peptide restricted to HLA-A*24:02;
- and
- (f)(3) the transformed cell according to (f)(1), which is a lymphocyte.
A nucleic acid comprising:
- (1) a cDNA sequence encoding a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 4;
- and (2) a cDNA sequence encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8.
A nucleic acid comprising:
- (1) a cDNA sequence encoding a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 14;
- and (2) a cDNA sequence encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15.
A cDNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8.
A cDNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15.
A vector comprising one of (a) to (d) below:
- (a) a DNA encoding a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 4, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8;
- (b) a DNA encoding a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 14, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15;
- (c) a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8;
- or
- (d) a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15.
A transformed cell comprising one of (a) to (d) below:
- (a) a DNA encoding a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 4, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8;
- (b) a DNA encoding a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 14, and a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15;
- (c) a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8;
- or
- (d) a DNA encoding a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15.
A transformed cell comprising a DNA encoding a T cell receptor α-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 4 and 14, and a DNA encoding a T cell receptor β-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 8 and 15, the transformed cell being detectable by a molecule multimerized by binding a wildtype WT1 peptide restricted to HLA-A*24:02 and a molecule multimerized by binding a mutant WT1 peptide restricted to HLA-A*24:02.
A kit for detecting any one of a wildtype WT1 peptide restricted to HLA-A*24:02 and a mutant WT1 peptide restricted to HLA-A*24:02, the kit comprising at least one of (a) to (c) below and instructions for using the kit:
- (a) a cDNA encoding a T cell receptor α-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 4 and 14, and a cDNA encoding a T cell receptor β-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 8 and 15;
- (b) a vector comprising a DNA encoding a T cell receptor α-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 4 and 14, and a DNA encoding a T cell receptor β-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 8 and 15;
- or
- (c)(1) a transformed cell comprising a DNA encoding a T cell receptor α-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 4 and 14, and a DNA encoding a T cell receptor β-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 8 and 15;
- or
- (c)(2) a transformed cell comprising a DNA encoding a T cell receptor α-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 4 and 14 and a DNA encoding a T cell receptor β-chain protein having any one of the amino acid sequences of SEQ ID NOs:
- 8 and 15, the transformed cell being detectable by a molecule multimerized by binding a wildtype WT1 peptide restricted to HLA-A*24:02 and a molecule multimerized by binding a mutant WT1 peptide restricted to HLA-A*24:02;
- and
- (c)(3) the transformed cell according to (c)(1), which is a lymphocyte.
Dependencies are inferred from the claim text.