Methods and pharmaceutical compositions for the treatment of cancer
The present invention relates to methods and pharmaceutical compositions for the treatment of cancer. In particular, the present invention relates to a polypeptide comprising or consisting of i) an amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1 or, ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1, or iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1 or, iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1.
1. A polypeptide which consists of:
i) an amino acid sequence ranging from a phenylalanine residue at position 380 to a leucine residue at position 384 in SEQ ID NO: 1, or
ii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1.
2. A polypeptide which consists of:
i) an amino acid sequence ranging from the phenylalanine residue at position 380 to an isoleucine residue at position 388 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the isoleucine residue at position 388 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the isoleucine residue at position 388 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the isoleucine residue at position 388 in SEQ ID NO:1.
3. A polypeptide which consists of:
i) an amino acid sequence ranging from the phenylalanine residue at position 380 to a leucine residue at position 391 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 391 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 391 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 391 in SEQ NO:1.
4. A polypeptide which consists of:
i) an amino acid sequence ranging from a tyrosine residue at position 379 to a leucine residue at position 391 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the tyrosine residue at position 379 to the leucine residue at position 391 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the tyrosine residue at position 379 to the leucine residue at position 391 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the tyrosine residue at position 379 to the leucine residue at position 391 in SEQ ID NO:1.
5. A polypeptide which consists of:
i) an amino acid sequence ranging from a glutamine residue at position 378 to a leucine residue at position 391 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from glutamine residue at position 378 to the leucine residue at position 391 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from glutamine residue at position 378 to the leucine residue at position 391 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from glutamine residue at position 378 to the leucine residue at position 391 in SEQ ID NO:1.
6. A polypeptide which consists of:
i) an amino acid sequence ranging from a leucine residue at position 377 to a leucine residue at position 391 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the leucine residue at position 377 to the leucine residue at position 391 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the leucine residue at position 377 to the leucine residue at position 391 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the leucine residue at position 377 to the leucine residue at position 391 in SEQ ID NO:1.
7. A polypeptide which consists of:
i) an amino acid sequence ranging from a lysine residue at position 371 to a glycine residue at position 397 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the lysine residue at position 371 to the glycine residue at position 397 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the lysine residue at position 371 to the glycine residue at position 397 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the lysine residue at position 371 to the glycine residue at position 397 in SEQ ID NO:1.
8. A polypeptide which consists of:
i) an amino acid sequence ranging from a lysine residue at position 371 to a leucine residue at position 391 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the lysine residue at position 371 to the leucine residue at position 391 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the lysine residue at position 371 to the leucine residue at position 391 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the lysine residue at position 371 to the leucine residue at position 391 in SEQ ID NO:1.
9. A polypeptide which consists of:
i) an amino acid sequence ranging from the phenylalanine residue at position 380 to a threonine residue at position 399 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the threonine residue at position 399 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the threonine residue at position 399 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the threonine residue at position 399 in SEQ ID NO:1.
10. A polypeptide which consists of:
i) an amino acid sequence ranging from a lysine residue at position 371 to a threonine residue at position 399 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the lysine residue at position 371 to the threonine residue at position 399 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the lysine residue at position 371 to the threonine residue at position 399 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the lysine residue at position 371 to the threonine residue at position 399 in SEQ ID NO:1.
11. A polypeptide which consists of:
i) an amino acid sequence ranging from a leucine residue at position 377 to a threonine residue at position 399 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the leucine residue at position 377 to the threonine residue at position 399 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the leucine residue at position 377 to the threonine residue at position 399 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso having at least 70% of identity with the amino acid sequence ranging from the leucine residue at position 377 to the threonine residue at position 399 in SEQ ID NO:1.
12. A fusion protein comprising
I. a polypeptide which consists of:
i) an amino acid sequence ranging from a phenylalanine residue at position 380 to a leucine residue at position 388 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 388 in SEQ ED NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 388 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 388 in SEQ ID NO:1, and
II. at least one heterologous polypeptide.
13. The fusion protein of claim 12 wherein the last amino acid of the C-terminal end of said polypeptide is directly linked by a covalent bond to the first amino acid of the N-terminal end of said at least one heterologous polypeptide, or the first amino acid of the N-terminal end of said polypeptide is directly linked by a covalent bond to the last amino acid of the C-terminal end of said at least one heterologous polypeptide.
14. The fusion protein of claim 12 wherein the heterologous polypeptide is a cell-penetrating peptide.
15. The fusion protein of claim 12 wherein the heterologous polypeptide is an internalization sequence derived either from the homeodomain of Drosophila Antennapedia/Penetratin (Antp) protein or the Transactivator of Transcription (TAT) cell penetrating sequence (SEQ ID NO: 12).
16. The fusion protein of claim 12 which comprises or consists of a sequence selected from the group consisting of SEQ ID NO:6; SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:16; and SEQ ID NO:17.
17. A method for treating a cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a) a polypeptide which consists of:
i) an amino acid sequence ranging from a phenylalanine residue at position 380 to a leucine residue at position 384 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO:1, or
b) a fusion protein comprising the polypeptide.
18. The method of claim 17 wherein the cancer is selected from the group consisting of breast cancer, triple-negative breast cancer, Acute Promyelocytic Leukemia (AML), hematologic cancer, lymphoma, B cell lymphoma, T cell lymphoma, B-cell non-Hodgkin's lymphoma, T-acute lymphoblastic leukemia, lung adenocarcinoma, kidney cancer, ovarian carcinoma, colon carcinoma, melanoma, and Sezary syndrome.
19. A pharmaceutical composition comprising
a polypeptide which consists of:
i) an amino acid sequence ranging from a phenylalanine residue at position 380 to a leucine residue at position 388 in SEQ ID NO:1, or
ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 388 in SEQ ID NO:1, or
iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 388 in SEQ ID NO:1, or
iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 388 in SEQ ID NO:1, or
a fusion protein comprising the polypeptide.