Anti-thyroglobulin T cell receptors
Disclosed is a synthetic T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of thyroglobulin (TG), TG 470-478 . Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the disclosure are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.
1. An isolated or purified T cell receptor (TCR) having antigenic specificity for the amino acid sequence of SEQ ID NO: 2 and comprising an α chain complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 3, an α chain CDR2 comprising the amino acid sequence of SEQ ID NO: 4, an α chain CDR3 comprising the amino acid sequence of SEQ ID NO: 5, a β chain CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a β chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a β chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8.
2. The isolated or purified TCR of claim 1 , comprising an α chain variable region comprising the amino acid sequence of SEQ ID NO: 9 and a β chain variable region comprising the amino acid sequence of SEQ ID NO: 10.
3. The isolated or purified TCR of claim 1 , further comprising an α chain constant region comprising the amino acid sequence of SEQ ID NO: 13 and a β chain constant region comprising the amino acid sequence of SEQ ID NO: 14.
4. The isolated or purified TCR of claim 1 , comprising an α chain comprising the amino acid sequence of SEQ ID NO: 11 and a β chain comprising the amino acid sequence of SEQ ID NO: 12.
5. The isolated or purified TCR of claim 1 , comprising a self-cleaving, viral linker peptide.
6. An isolated or purified polypeptide comprising a functional portion of the TCR of claim 1 , wherein the functional portion comprises the amino acid sequences of SEQ ID NOs: 3-8.
7. The isolated or purified polypeptide of claim 6 , comprising a self-cleaving, viral linker peptide.
8. An isolated or purified protein comprising at least one of the polypeptides of claim 6 .
9. An isolated or purified polypeptide comprising a functional portion of the TCR of claim 1 , wherein the functional portion comprises the amino acid sequence of both SEQ ID NOs: 9 and 10.
10. An isolated or purified polypeptide comprising a functional portion of the TCR of claim 1 , wherein the functional portion comprises the amino acid sequence of both SEQ ID NOs: 11 and 12.
11. A pharmaceutical composition comprising the TCR according to claim 1 and a pharmaceutically acceptable carrier.
12. An isolated or purified protein comprising a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 3-5 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 6-8.
13. The isolated or purified protein according to claim 12 , comprising a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 9 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 10.
14. The isolated or purified protein according to claim 12 , comprising a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 11 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 12.
15. The isolated or purified protein according to claim 12 , wherein the protein is a fusion protein.
16. The isolated or purified protein according to claim 12 , wherein the protein is a recombinant antibody.
17. The isolated or purified protein according to claim 12 , comprising a self-cleaving, viral linker peptide.
18. An isolated or purified nucleic acid comprising a nucleotide sequence encoding the TCR according to claim 1 .
19. The nucleic acid according to claim 18 , comprising the nucleotide sequences of SEQ ID NOs: 22-27.
20. The nucleic acid according to claim 18 , comprising the nucleotide sequences of SEQ ID NOs: 15 and 16.
21. The nucleic acid according to claim 18 , further comprising the nucleotide sequences of SEQ ID NOs: 19 and 20.
22. The nucleic acid according to claim 18 , comprising the nucleotide sequences of SEQ ID NOs: 17 and 18.
23. A recombinant expression vector comprising the nucleic acid according to claim 18 .
24. The recombinant expression vector according to claim 23 comprising the nucleotide sequence of SEQ ID NO: 21.
25. An isolated host cell comprising the recombinant expression vector of claim 23 .
26. The host cell according to claim 25 , wherein the cell is human.
27. A population of cells comprising at least one host cell of claim 25 .