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US 2014/0212888 A1Published application
T cell receptor and uses thereof
AssigneeMedical & Biological Laboratories Co., Ltd.
InventorsKazue WATANABE, Shingo TOJI
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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.
Claims22
An isolated T cell receptor complex comprising:
- a T cell receptor α-chain protein having amino acid sequences of SEQ ID NOs:
- 1 to 3;
- and
- a T cell receptor β-chain protein having amino acid sequences of SEQ ID NOs:
- 5 to 7.
2 more elements
An isolated T cell receptor α-chain protein having amino acid sequences of SEQ ID NOs:
- 1 to 3.
An isolated T cell receptor β-chain protein having amino acid sequences of SEQ ID NOs:
- 5 to 7.
A vector comprising and being capable of expressing a DNA of any one of (a) to (c) below:
- (a) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- (b) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- and
- (c) the DNA according to (a) and (b).
3 more elements
A transformed cell comprising a DNA of any one of (a) to (c) below:
- (a) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- (b) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- and
- (c) the DNA according to (a) and (b).
3 more elements
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.
An isolated antibody capable of specifically binding to a molecule of any one of (a) to (c) below:
- (a)(1) a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3,
- (a)(2) a T cell receptor α-chain protein which has the amino acid sequence of SEQ ID NO:
- 4,
- (a)(3) a T cell receptor α-chain protein, which has the amino acid sequence of SEQ ID NO:
- 14;
- (b)(1) a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7,
- (b)(2) a T cell receptor β-chain protein which has the amino acid sequence of SEQ ID NO:
- 8,
- (b)(3) a T cell receptor β-chain protein which has the amino acid sequence of SEQ ID NO:
- 15;
- (c)(1) a T cell receptor complex comprising:
- a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- and
- a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7,
- (c)(2) a T cell receptor complex comprising:
- a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 4;
- and
- a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8,
- (c)(3) a T cell receptor complex comprising:
- a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 14;
- and
- a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15, and
- (c)(4) a T cell receptor complex which is capable of recognizing a wildtype WT1 peptide restricted to HLA-A*24:02 and a mutant WT1 peptide restricted to HLA-A*24:02.
28 more elements
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 component of (a) to (h) below:
- (a)(1) a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3,
- (a)(2) a T cell receptor α-chain protein which has the amino acid sequence of SEQ ID NO:
- 4,
- (a)(2) a T cell receptor α-chain protein which has the amino acid sequence of SEQ ID NO:
- 14;
- (b)(1) a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7,
- (b)(2) a T cell receptor β-chain protein which has the amino acid sequence of SEQ ID NO:
- 8,
- (b)(3) a T cell receptor β-chain protein which has the amino acid sequence of SEQ ID NO:
- 15;
- (c)(1) a T cell receptor complex comprising:
- a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- and
- a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7,
- (c)(2) a T cell receptor complex comprising:
- a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 4;
- and
- a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 8,
- (c)(3) a T cell receptor complex comprising:
- a T cell receptor α-chain protein having the amino acid sequence of SEQ ID NO:
- 14;
- and
- a T cell receptor β-chain protein having the amino acid sequence of SEQ ID NO:
- 15,
- (c)(4) a T cell receptor complex which is capable of recognizing a wildtype WT1 peptide restricted to HLA-A*24:02 and a mutant WT1 peptide restricted to HLA-A*24:02;
- (d)(1) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- (d)(2) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- (e) a vector comprising and being capable of expressing a DNA of any one of (a′) to (c′) below:
- (a′) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- (b′) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- and
- (c′) the DNA according to (a) and (b);
- (f)(1) a transformed cell comprising a DNA of any one of (a″) to (c″) below:
- (a″) a DNA encoding a T cell receptor α-chain protein having the amino acid sequences of SEQ ID NOs:
- 1 to 3;
- (b″) a DNA encoding a T cell receptor β-chain protein having the amino acid sequences of SEQ ID NOs:
- 5 to 7;
- and
- (c″) the DNA according to (a) and (b);
- (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;
- (f)(3) the transformed cell according to (f)(1), which is a lymphocyte;
- (g) an antibody capable of specifically binding to a molecule of any one of (a)(1)-(a)(3), (b)(1)-(b)(3) and (c)(1)-(c)(4);
- and
- (h) a molecule multimerized by binding an isolated T cell receptor complex of (c)(1).
53 more elements
Dependencies are inferred from the claim text.