T cell immunotherapy specific for WT-1

1. An isolated polynucleotide encoding a binding protein, comprising a polynucleotide encoding a human TCR α-chain variable (V α ) domain that contains the complementarity determining region 3 (CDR3) amino acid sequence of SEQ ID NO.:25 or 26, the CDR1 amino acid sequence of SEQ ID NO: 23, and the CDR2 amino acid sequence of SEQ ID NO: 24, wherein the polynucleotide encoding the V α domain is at least 80% identical to the nucleotide sequence of SEQ ID NO 78, 128 or 80, provided that the Vα domain comprises the CDR3 of SEQ ID NO:25 or 26, the CDR1 of SEQ ID NO:23 and the CDR2 of SEQ ID NO:24; and a polynucleotide encoding a human TCR β-chain variable (V β ) domain that contains the CDR3 amino acid sequence of SEQ ID NO.:29, the CDR1 amino acid sequence of SEQ ID NO:27, and the CDR2 amino acid sequence of SEQ ID NO:28, wherein the polynucleotide encoding the V β domain is at least 80% identical to the nucleotide sequence of SEQ ID NO. 89, provided that the Vβ domain comprises the CDR3 of SEQ ID NO:29, the CDR1 of SEQ ID NO:27 and the CDR2 of SEQ ID NO:28; and wherein the encoded binding protein specifically binds to a RMFPNAPYL (SEQ ID NO.:16):human leukocyte antigen-A*201 (HLA-A*201) complex.

2. The isolated polynucleotide of claim 1 , wherein the encoded V α domain has at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:1 or 2.

3. The isolated polynucleotide of claim 2 , wherein:

(a) the V α domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:78, 128, or 80; or

(b) the V α domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:78, 128, or 80.

4. The isolated polynucleotide of claim 1 , wherein the encoded V β domain has at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:9.

5. The isolated polynucleotide of claim 4 , wherein:

(a) the V β domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:89; or

(b) the V β domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:89.

6. The isolated polynucleotide of claim 1 , wherein the V α domain encoding polynucleotide comprises a polynucleotide encoding an α-chain constant domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:3 or 4 and the polynucleotide encoding the α-chain constant domain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:82 or 84.

7. The isolated polynucleotide of claim 6 , wherein:

(a) the α-chain constant domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:82 or 84; or

(b) the α-chain constant domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:82 or 84.

8. The isolated polynucleotide of claim 1 , wherein the V β domain encoding polynucleotide comprises a polynucleotide encoding a β-chain constant domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:10 or 11 and the polynucleotide encoding the β-chain constant domain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:92 or 93.

9. The isolated polynucleotide of claim 8 , wherein:

(a) the β-chain constant domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:92 or 93; or

(b) the β-chain constant domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:92 or 93.

10. The isolated polynucleotide of claim 1 , wherein the V α domain encoding polynucleotide comprises a polynucleotide encoding an α-chain constant domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:3 or 4 and the polynucleotide encoding the α-chain constant domain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:82 or 84; and the V β domain encoding polynucleotide comprises a polynucleotide encoding a β-chain constant domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:10 or 11 and the polynucleotide encoding the β-chain constant domain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:92 or 93.

11. The isolated polynucleotide of claim 10 , wherein:

(a) the α-chain constant domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:82 or 84; or

(b) the α-chain constant domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:82 or 84.

12. The isolated polynucleotide of claim 10 , wherein:

(a) the β-chain constant domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:92 or 93; or

(b) the β-chain constant domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:92 or 93.

13. The isolated polynucleotide of claim 10 , wherein:

(i) (a) the α-chain constant domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:82 or 84; or

(b) the α-chain constant domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:82 or 84; and

(ii) (a) the β-chain constant domain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:92 or 93; or

(b) the β-chain constant domain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:92 or 93.

14. The isolated polynucleotide of claim 1 , wherein the V α domain encoding polynucleotide is contained in a polynucleotide encoding a T cell receptor (TCR) α-chain having at least 90% sequence identity to the amino acid sequence of any one of SEQ ID NOS.:5-8 and the polynucleotide encoding the TCR α-chain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:86 or 87.

15. The isolated polynucleotide of claim 14 , wherein:

(a) the TCR α-chain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:86 or 87; or

(b) the TCR α-chain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:86 or 87.

16. The isolated polynucleotide of claim 1 , wherein the V β domain encoding polynucleotide is contained in a polynucleotide encoding a TCR β-chain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:12 or 13 and the polynucleotide encoding the TCR β-chain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:95.

17. The isolated polynucleotide of claim 16 , wherein:

(a) the TCR β-chain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:95; or

(b) the TCR β-chain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:95.

18. The isolated polynucleotide of claim 1 , wherein the V α domain encoding polynucleotide is contained in a polynucleotide encoding a TCR α-chain having at least 90% sequence identity to the amino acid sequence of any one of SEQ ID NOS.:5-8 and the polynucleotide encoding the TCR α-chain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:86 or 87; and the V β domain encoding polynucleotide is contained in a polynucleotide encoding a TCR β-chain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO.:12 or 13 and the polynucleotide encoding the TCR β-chain is at least 80% identical to the nucleotide sequence of SEQ ID NO.:95.

19. The isolated polynucleotide of claim 18 , wherein:

(i) (a) the TCR α-chain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:86; or

(b) the TCR α-chain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:86; and

(ii) (a) the TCR β-chain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:95; or

(b) the TCR β-chain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:95.

20. The isolated polynucleotide of claim 18 , wherein:

(i) (a) the TCR α-chain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:87; or

(b) the TCR α-chain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:87; and

(ii) (a) the TCR β-chain encoding polynucleotide comprises the nucleotide sequence of SEQ ID NO.:95; or

(b) the TCR β-chain encoding polynucleotide consists of the nucleotide sequence of SEQ ID NO.:95.

21. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes a self-cleaving peptide disposed between the V α domain encoding polynucleotide and the V β domain encoding polynucleotide.

22. The isolated polynucleotide of claim 21 , wherein the polynucleotide has a structure from 5′-end to 3′-end of (V α domain encoding polynucleotide)-(self-cleaving peptide)-(V β domain encoding polynucleotide) or (V β domain encoding polynucleotide)-(self-cleaving peptide)-(V α domain encoding polynucleotide).

23. The isolated polynucleotide of claim 21 , wherein the encoded self-cleaving peptide has at least 90% sequence identity to the amino acid sequence of any one of SEQ ID NOS.:17-20 and the polynucleotide encoding the self-cleaving peptide is at least 80% identical to the nucleotide sequence of any one of SEQ ID NOS.:98-102, respectively.

24. The isolated polynucleotide of claim 18 , wherein the polynucleotide encodes a self-cleaving peptide disposed between the TCR α-chain encoding polynucleotide and the TCR β-chain encoding polynucleotide.

25. The isolated polynucleotide of claim 24 , wherein the polynucleotide has a structure from 5′-end to 3′-end of (V α domain encoding polynucleotide)-(self-cleaving peptide)-(V β domain encoding polynucleotide) or (V β domain encoding polynucleotide)-(self-cleaving peptide)-(V α domain encoding polynucleotide).

26. The isolated polynucleotide of claim 24 , wherein the encoded self-cleaving peptide has at least 90% sequence identity to the amino acid sequence of any one of SEQ ID NOS.:17-20 and the polynucleotide encoding the self-cleaving peptide is at least 80% identical to the nucleotide sequence of any one of SEQ ID NOS.:98-102, respectively.

27. The isolated polynucleotide of claim 21 , wherein:

(a) the polynucleotide encoding the V α domain, the self-cleaving peptide, and the V β domain comprises the nucleotide sequence of SEQ ID NO.:96 or 97; or

(b) the polynucleotide encoding the V α domain, the self-cleaving peptide, and the V β domain consists of the nucleotide sequence of SEQ ID NO.:96 or 97.

28. The isolated polynucleotide of claim 1 , wherein the binding protein is a T cell receptor (TCR), a chimeric antigen receptor or an antigen-binding fragment of a TCR.

29. The isolated polynucleotide of claim 1 , wherein the binding protein is a TCR and the TCR binds to a RMFPNAPYL (SEQ ID NO.:16):human leukocyte antigen (HLA) complex with a K d less than or equal to about 8 nM or less than or equal to about 5 nM.

30. An expression vector, comprising a polynucleotide of claim 1 operably linked to an expression control sequence.

31. The expression vector of claim 30 , wherein the vector is capable of delivering the polynucleotide to a host cell.

32. The expression vector of claim 31 , wherein the host cell is a hematopoietic progenitor cell or a human immune system cell.

33. The expression vector according to claim 32 , wherein the immune system cell is a T cell, a natural killer cell, a dendritic cell, or any combination thereof.

34. The expression vector according to claim 33 , wherein the T cell is a naïve T cell, a central memory T cell, an effector memory T cell, or any combination thereof.

35. The expression vector according of claims 31 , wherein the vector is a viral vector.

36. The expression vector according to claim 35 , wherein the viral vector comprises a lentiviral vector or a retroviral vector.

37. A recombinant host cell, comprising an expression vector of claim 30 , wherein the host cell expresses on its cell surface the binding protein encoded by the polynucleotide.

38. An isolated polynucleotide encoding a binding protein, comprising a polynucleotide encoding a human TCR α chain variable (Vα) domain, wherein the polynucleotide encoding the Vα domain comprises the nucleotide sequence of SEQ ID NO.:128; and a polynucleotide encoding a human TCR β chain variable (Vβ) domain, wherein the polynucleotide encoding the Vβ domain comprises the nucleotide sequence of SEQ ID NO.:89.

39. The isolated polynucleotide of claim 38 , wherein the polynucleotide encoding the Vα domain consists of the nucleotide sequence of SEQ ID NO.:128 and the polynucleotide encoding the Vβ domain consists of the nucleotide sequence of SEQ ID NO.:89.

40. The isolated polynucleotide of claim 38 , further comprising:

(a) a polynucleotide encoding an α-chain constant domain that:

(i) comprises the nucleotide sequence of SEQ ID NO:84; or

(ii) consists of the nucleotide sequence of SEQ ID NO:84;

(b) a polynucleotide encoding a β-chain constant domain that:

(i) comprises the nucleotide sequence of SEQ ID NO:93; or

(ii) consists of the nucleotide sequence of SEQ ID NO:93; or

(c) a polynucleotide of (a)(i) or (a)(ii), and a polynucleotide of (b)(i) or (b)(ii).

41. The isolated polynucleotide of claim 39 , further comprising:

(a) a polynucleotide encoding an α-chain constant domain that:

(i) comprises of the nucleotide sequence of SEQ ID NO:84; or

(ii) consists of the nucleotide sequence of SEQ ID NO:84;

(b) a polynucleotide encoding a β-chain constant domain that:

(i) comprises the nucleotide sequence of SEQ ID NO:93; or

(ii) consists of the nucleotide sequence of SEQ ID NO:93; or

(c) a polynucleotide of (a)(i) or (a)(ii), and a polynucleotide of (b)(i) or (b)(ii).

42. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:96.

43. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:97.

44. The isolated polynucleotide of claim 38 , wherein the encoded binding protein is a T cell receptor (TCR), a chimeric antigen receptor, or an antigen-binding fragment of a TCR.

45. The isolated polynucleotide of claim 1 , wherein the encoded V α domain has at least 90% identity to the amino acid sequence set forth in SEQ ID NO:1 or 2 and the encoded V β has at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9.

46. The isolated polynucleotide of claim 1 , wherein the encoded V α domain has at least 95% identity to the amino acid sequence set forth in SEQ ID NO:1 or 2 and the encoded V β has at least 95% identity to the amino acid sequence set forth in SEQ ID NO:9.

47. The isolated polynucleotide of claim 1 , wherein the encoded V α domain comprises the amino acid sequence set forth in SEQ ID NO:1 or 2 and the encoded V β comprises the amino acid sequence set forth in SEQ ID NO:9.