Peptides derived from transient receptor potential cation channel subfamily M member 1 (TRPM1), complexes comprising such peptides bound to MHC molecules
The present invention relates to novel peptides derived from Transient receptor potential cation channel subfamily M member 1 (TRPM1), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.
1. A method of treating cancer in a subject, comprising:
administering to the subject a therapeutically effective amount of a binding moiety capable of specifically binding a polypeptide
wherein the polypeptide comprises:
(a) the amino acid sequence of any one of SEQ ID NOS: 1-16, or
(b) the amino acid sequence of any one of SEQ ID NOs: 1-16 with the exception of 1, 2 or 3 amino acid substitutions and/or 1, 2 or 3 amino acid insertions, and/or 1, 2 or 3 amino acid deletions, and
wherein the polypeptide is capable of forming a complex with a Major Histocompatibility Complex (MHC) molecule.
2. The method of claim 1 , wherein the polypeptide is 8 to 16 amino acids in length.
3. The method of claim 2 , wherein the polypeptide is 9 amino acids in length.
4. The method of claim 3 , wherein the polypeptide has the amino acid sequence of SEQ ID NO: 12.
5. The method of claim 1 , wherein the cancer is uveal melanoma.
6. The method of claim 1 , wherein the binding moiety is capable of specifically binding the polypeptide when it is in complex with the MHC molecule.
7. The method of claim 6 , wherein the MHC molecule is MHC class I.
8. The method of claim 7 , wherein the MHC class I molecule is HLA-A*02.
9. The method of claim 1 , wherein the binding moiety is a T cell receptor (TCR) or an antibody.
10. The method of claim 9 , wherein the binding moiety is a TCR.
11. The method of claim 10 , wherein the TCR is a heterodimeric TCR comprising an alpha chain and a beta chain.
12. The method of claim 11 , wherein the alpha chain and the beta chain of the heterodimeric TCR each comprises a variable region and a constant region.
13. The method of claim 12 , wherein each variable region comprises three hypervariable complementarity determining regions (CDRs) embedded in a framework sequence: CDR1, CDR2, and CDR3.
14. The method of claim 10 , wherein the TCR is on the surface of a cell.
15. The method of claim 6 , wherein the binding moiety and/or the complex is conjugated to a detectable label.
16. The method of claim 15 , wherein the detectable label is selected from biotin, fluorescent streptavidin, a fluorescent or luminescent label, a radiolabel, or a peptide tag.
17. The method of claim 16 , wherein the peptide tag is selected from a FLAG tag, a MYC tag, an HA tag, a GST tag, a Strep tag, or a poly-histidine (His) tag.
18. A method of treating uveal melanoma, comprising:
administering to the subject a therapeutically effective amount of an heterodimeric TCR capable of specifically binding a polypeptide having the sequence of SEQ ID NO: 12 in complex with HLA-A*02.