- Document Number:
20210030838
- Appl. No:
16/638162
- Application Filed:
September 20, 2018
- نبذة مختصرة :
The present invention relates to peptides which are capable of potentiating the chemotactic potential of glycosaminoglycan binding chemokines, and to the use of said chemotaxis-potentiating peptides in the treatment of cancer.
- Claim:
1. A polypeptide for use in the treatment of cancer or for potentiating immune activation in a tumor or for potentiating the chemotactic potential of CCL21 having a length of less than 100 amino acids comprising or consisting of an amino acid sequence selected from the group consisting of a) the amino acid sequence according to SEQ ID NO: 1, b) a variant of SEQ ID NO: 1, wherein said variant has at least 80%, such as at least 90%, such as at least 95% sequence identity to SEQ ID NO: 1, but less than 99% sequence identity to SEQ ID NO: 1; c) a variant of SEQ ID NO: 1, wherein said variant has between 1 and 10 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2, 3, 4 or 5 amino acid substitutions relative to SEQ ID NO: 1; d) a fragment of SEQ ID NO: 1 having a length of at least 10 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; e) an amino acid sequence differing from SEQ ID NO: 1 by truncation at the N-terminus by at least one amino acid, such as between 1-20 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; f) an amino acid sequence differing from SEQ ID NO: 1 by truncation at the C-terminus by at least one amino acid, such as between 1-19 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; and g) an amino acid sequence differing from SEQ ID NO: 1 by truncation at the N-terminus by at least one amino acid, such as between 1-20 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, and at the C-terminus by at least one amino acid, such as between 1-19 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, wherein said polypeptide has a length of at least 10 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; wherein said polypeptide is capable of binding to glycosaminoglycans (GAGs).
- Claim:
2. The polypeptide for use according to claim 1, wherein said polypeptide has a length of less than 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20 or 15 amino acids.
- Claim:
3. The polypeptide for use according to any of the preceding claims, wherein the polypeptide has a length of at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 amino acids.
- Claim:
4. The polypeptide for use according to any of the preceding claims, wherein the amino acid substitutions are conservative substitutions.
- Claim:
5. The polypeptide for use according to any of the preceding claims, wherein the amino acid substitutions increase the net charge of said polypeptide.
- Claim:
6. The polypeptide for use according to any of the preceding claims, wherein the amino acid substitutions are substitutions of negative or neutral amino acid residues to positive amino acid residues.
- Claim:
7. The polypeptide for use according to any of the preceding claims, wherein the amino acid substitutions are substitutions of negative amino acid residues to neutral or positive amino acid residues.
- Claim:
8. The polypeptide for use according to any of the preceding claims, wherein said polypeptide comprises one or more moieties conjugated to said polypeptide, optionally wherein the polypeptide and the one or more moieties are conjugated to each other by a linker.
- Claim:
9. The polypeptide for use according to claim 8, wherein the one or more moieties are selected from the group consisting of albumin, fatty acids, polyethylene glycol (PEG), acylation groups, antibodies and antibody fragments.
- Claim:
10. The polypeptide for use according to claim 8, wherein the one or more moieties selected from the group consisting proteins, peptides and receptor ligands.
- Claim:
11. The polypeptide for use according to any of the preceding claims, wherein said polypeptide is administered in combination with an anti-cancer agent, such as for example cyclophosphamide, Paclitaxel, 5-fluorouracil, CTLA-4 antagonists, PD-L1 antagonists or PD-1 antagonists.
- Claim:
12. The polypeptide for use according to any of the preceding claims, wherein said polypeptide is administered in combination with radiation therapy.
- Claim:
13. The polypeptide for use according to any of the preceding claims, wherein said polypeptide is administered in combination with cell-based anticancer immunotherapy.
- Claim:
14. The polypeptide for use according to any of the preceding claims, wherein said polypeptide is administered in combination with a cytokine, such as for example CCL21, INF-γ, IL-2, CXCL9, CXCL10 or CXCL12.
- Claim:
15. The polypeptide for use according to any of the preceding claims, wherein said polypeptide is administered in combination with CCL21.
- Claim:
16. The polypeptide for use according to any of the preceding claims, wherein the cancer is a CCR7-positive cancer.
- Claim:
17. An isolated polypeptide having a length of less than 100 amino acids comprising or consisting of an amino acid sequence selected from the group consisting of a) the amino acid sequence according to SEQ ID NO: 1, b) a variant of SEQ ID NO: 1, wherein said variant has at least 80%, such as at least 90%, such as at least 95% sequence identity to SEQ ID NO: 1, but less than 99% sequence identity to SEQ ID NO: 1; c) a variant of SEQ ID NO: 1, wherein said variant has between 1 and 10 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2, 3, 4 or 5 amino acid substitutions relative to SEQ ID NO: 1; d) a fragment of SEQ ID NO: 1 having a length of at least 10 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; e) an amino acid sequence differing from SEQ ID NO: 1 by truncation at the N-terminus by at least one amino acid, such as between 1-20 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; f) an amino acid sequence differing from SEQ ID NO: 1 by truncation at the C-terminus by at least one amino acid, such as between 1-19 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; and g) an amino acid sequence differing from SEQ ID NO: 1 by truncation at the N-terminus by at least one amino acid, such as between 1-20 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, and at the C-terminus by at least one amino acid, such as between 1-19 amino acids, such as between 1-15 amino acids, for example between 1-10 amino acids, such as between 1-5 amino acids, wherein said polypeptide has a length of at least 10 amino acids, or a variant thereof having between 1 and 5 amino acid substitutions relative to SEQ ID NO: 1, such as 1, 2 or 3 amino acid substitutions relative to SEQ ID NO: 1; wherein said polypeptide is capable of binding to glycosaminoglycans (GAGs).
- Claim:
18. The polypeptide according to claim 17, wherein said polypeptide consists of an amino acid sequence according to any one of SEQ ID NOs: 1-33, or a variant thereof having at least 80% sequence identity, such as at least 90%, such as at least 95% sequence identity to said sequence and having at least one amino acid substitution relative thereto, such as 1, 2 or 3 amino acid substitutions.
- Claim:
19. The polypeptide according to claim 17, wherein said polypeptide consists of an amino acid sequence according to any of SEQ ID NOs: 2, 3, or 5-33 or a variant of any of said sequences, wherein said variant has at least 80% sequence identity to said sequence, such as at least 90%, such as at least 95% sequence identity to said sequence, and wherein said sequence comprises at least one amino acid substitution relative to said sequence, such as 1, 2 or 3 amino acid substitutions.
- Claim:
20. The polypeptide according to any of claims 17-19, wherein said polypeptide has a length of less than 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20 or 15 amino acids.
- Claim:
21. The polypeptide according to any of claims 17 to 20, wherein the polypeptide has a length of at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 amino acids.
- Claim:
22. The polypeptide according to any of claims 17 to 21, wherein the amino acid substitutions are conservative substitutions.
- Claim:
23. The polypeptide according to any of claims 17 to 22, wherein the amino acid substitutions increase the net charge of said polypeptide.
- Claim:
24. The polypeptide according to claim 23, wherein the amino acid substitutions are substitutions of negative or neutral amino acid residues to positive amino acid residues.
- Claim:
25. The polypeptide according to claim 23, wherein the amino acid substitutions are substitutions of negative amino acid residues to neutral or positive amino acid residues.
- Claim:
26. The polypeptide according to any of claims 17 to 25, wherein said polypeptide comprises one or more moieties conjugated to said polypeptide, optionally wherein the polypeptide and the one or more moieties are conjugated to each other by a linker.
- Claim:
27. The polypeptide according to claim 26, wherein the one or more moieties are selected from the group consisting of albumin, fatty acids, polyethylene glycol (PEG), acylation groups, antibodies and antibody fragments.
- Claim:
28. An isolated polynucleotide encoding the polypeptide according to any of claims 17 to 27.
- Claim:
29. A vector comprising the polynucleotide according to claim 28.
- Claim:
30. The vector according to claim 29, wherein the vector is a viral vector, selected from the group consisting of adenoviruses, lentiviruses, adeno-associated viruses, herpesviruses, vaccinia viruses, poxviruses and oncolytic viruses.
- Claim:
31. The vector according to claim 29, wherein the vector is an expression vector, such as an expression vector selected from the group consisting of E. coli expression vector and SF9-insect expression vectors.
- Claim:
32. A host cell comprising the polynucleotide according to claim 28 and/or the vector according to any of claims 29 to 31.
- Claim:
33. A pharmaceutical composition comprising the polypeptide according to any of claims 17 to 27, the isolated polynucleotide according to claim 28, the vector according to any of claims 29 to 31, or the host cell according to claim 32.
- Claim:
34. The pharmaceutical composition according to claim 33, wherein the polypeptide according to any of claims 17 to 27, the isolated polynucleotide according to claim 28, the vector according to any of claims 29 to 31, or the host cell according to claim 32 is formulated in a nanoparticle.
- Claim:
35. The polypeptide according to any of claims 17 to 27, the isolated polynucleotide according to claim 28, the vector according to any of claims 29 to 31, or the host cell according to claim 32 for use as a medicament.
- Claim:
36. The polypeptide according to any of claims 17 to 27, the isolated polynucleotide according to claim 28, the vector according to any of claims 29 to 31, or the host cell according to claim 32 for use in the manufacture of a medicament for treatment of cancer.
- Current International Class:
61; 61; 61; 61
- الرقم المعرف:
edspap.20210030838
No Comments.