Treatment of haematological malignancies

1. An isolated nucleic acid sequence comprising a promoter operably linked to a nucleic acid sequence encoding:

(a) a polypeptide comprising a CDR3 of a TCR α chain polypeptide that specifically binds to the peptide CLAVEEVSL (SEQ ID NO:1) and/or

(b) a polypeptide comprising a CDR3 of a TCR β chain polypeptide that specifically binds to the peptide CLAVEEVSL (SEQ ID NO:1),

wherein the isolated nucleic acid sequence is cDNA.

2. The isolated nucleic acid sequence of claim 1 , wherein the nucleic acid sequence encodes both (a) and (b), and wherein (a) and (b) together specifically bind to the peptide CLAVEEVSL (SEQ ID NO:1).

3. The isolated nucleic acid sequence of claim 1 , wherein:

(i) the CDR3 of (a) has an amino acid sequence having at least 90% sequence identity to CAVTGARLMF (SEQ ID NO:2);

(ii) the CDR3 of (a) is encoded by the nucleic acid sequence of SEQ ID NO: 3 or SEQ ID NO:4;

(iii) the CDR3 of (b) has an amino acid sequence having at least 90% sequence identity to CASSPGGLSNEQF (SEQ ID NO:5);

(iv) the CDR3 of (b) is encoded by the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO:7;

(v) the CDR3 of (a) is within a TCR α chain variable region that specifically binds to SEQ ID NO:1, optionally wherein (a) further comprises a TCR α chain constant region; optionally wherein the TCR α chain variable region has an amino acid sequence having at least 90% sequence identity to SEQ ID NO:8, and optionally wherein the TCR α chain variable region of (a) is encoded by the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO:10;

(vi) the CDR3 of (b) is within a TCR β chain variable region that specifically binds to SEQ ID NO:1, optionally wherein (b) further comprises a TCR β chain constant region, optionally wherein the TCR β chain variable region has an amino acid sequence having at least 90% sequence identity to SEQ ID NO:11, and optionally wherein the TCR β chain variable region of (b) is encoded by the nucleic acid sequence of SEQ ID NO: 12 or SEQ ID NO:13;

(vii) the CDR3 of (a) is within a TCR α chain variable region having at least 90% sequence identity to SEQ ID NO:8, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 2; and optionally wherein (a) comprises a TCR α chain constant region, and optionally wherein the TCR α chain variable region CDR1 has an amino acid sequence of SEQ ID NO:14 and the TCR α chain variable region CDR2 has an amino acid sequence of SEQ ID NO:15; and/or

(viii) the CDR3 of (b) is within a TCR β chain variable region having at least 90% sequence identity to SEQ ID NO:11, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 5; and optionally wherein (b) comprises a TCR β chain constant region, and optionally wherein the TCR β chain variable region CDR1 has an amino acid sequence of SEQ ID NO:16 and the TCR β chain variable region CDR2 has an amino acid sequence of SEQ ID NO:17.

4. The isolated nucleic acid sequence of claim 1 , wherein the peptide CLAVEEVSL (SEQ ID NO:1) is cysteinylated.

5. The isolated nucleic acid sequence of claim 1 , wherein the nucleic acid sequence encodes a T cell receptor.

6. A vector comprising the nucleic acid sequence of claim 1 .

7. The vector of claim 6 , wherein the vector is a plasmid or a viral vector, optionally wherein the vector is selected from the group consisting of a retrovirus, lentivirus, adeno-associated virus, adenovirus, vaccinia virus, canary poxvirus, herpes virus, minicircle vector, synthetic DNA, and synthetic RNA.

8. A modified cell transfected or transduced with the nucleic acid sequence of claim 1 or a vector comprising the nucleic acid sequence of claim 1 .

9. The modified cell of claim 8 , wherein the modified cell is selected from the group consisting of a CD8 T cell, a CD4 T cell, a NK cell, a NKT cell, a gamma-delta T cell, a hematopoietic stem cell, a progenitor cell, a T cell line and a NK-92 cell line, and optionally wherein the modified cell is a human cell.

10. A pharmaceutical composition for treating or preventing a ΔNPM1 positive haematological malignancy, comprising

(a) the nucleic acid sequence of claim 1 , a vector comprising the nucleic acid sequence of claim 1 , or a modified cell comprising the nucleic acid sequence of claim 1 , and

(b) a pharmaceutically acceptable excipient, adjuvant, diluent and/or carrier.

11. A method of treating or preventing a ΔNPM1 positive haematological malignancy in a human subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 10 .

12. The method of claim 11 , wherein the haematological malignancy is a myeloid malignancy, and optionally wherein the myeloid malignancy is acute myeloid leukemia.

13. The method of claim 11 , wherein the method induces or enhances a cell mediated immune response in the subject.

14. A method of generating a T cell receptor, comprising contacting a nucleic acid sequence of claim 1 with a cell under conditions in which the nucleic acid sequence is incorporated and expressed by the cell to generate the T cell receptor that specifically binds to the peptide of SEQ ID NO:1.

15. The method of claim 14 , wherein the method is ex vivo.