Chemokine binding polypeptides capable of inhibiting the course of autoimmunity, inflammation and cancer
Novel polypeptides comprising a chemokine-binding peptide and an Fc fragment are disclosed. The polypeptides are capable of binding to certain chemokines so as to modulate their activity. These polypeptides can be used to modulate in vivo chemokine-dependent processes such as inflammation and autoimmunity, and to treat associated conditions.
1. An isolated polypeptide comprising at least one chemokine-binding peptide attached to an Fc domain or a fragment of said Fc domain, wherein said chemokine-binding peptide has the amino acid sequence as set forth in SEQ ID NO: 101, wherein the isolated polypeptide further comprises a signal peptide and wherein said signal peptide comprises an IL-6 signal peptide.
2. The polypeptide of claim 1 , further comprising a linker.
3. The polypeptide of claim 2 , wherein said linker is composed of 4 to 10 amino acids.
4. The polypeptide of claim 1 , wherein said linker is an amino acid linker.
5. The polypeptide of claim 1 , wherein said polypeptide inhibits binding of at least one chemokine to a chemokine receptor.
6. A pharmaceutical composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.
7. The pharmaceutical composition of claim 6 , formulated for intravenous administration, oral administration, sub-cutaneous administration, topical administration and/or intranasal administration.
8. The polypeptide of claim 1 wherein said polypeptide modulates a biological effect of a chemokine.
9. The polypeptide of claim 8 , wherein said chemokine is selected from the group consisting of Interferon-inducible T-cell alpha chemoattractant (I-TAC), Interferon gamma-induced protein 10 (IP-10), Monokine induced by gamma interferon (MIG), monocyte chemotactic protein-1 (MCP-1), eotaxin and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES).
10. The polypeptide of claim 8 , wherein said biological effect is selected from the group consisting of an inflammatory effect, cell migration, tumor growth, and cancer metastasis.
11. A conjugate comprising the polypeptide of claim 1 attached to a water-soluble polymer.
12. The conjugate of claim 11 , wherein said water-soluble polymer is polyethylene glycol.
13. An isolated polypeptide comprising at least one chemokine-binding peptide attached to an Fe domain or a fragment of said Fc domain, wherein said chemokine-binding peptide has the amino acid sequence as set forth in SEQ ID NO: 101, wherein the polypeptide further comprises a signal peptide and wherein the polypeptide has the formula:
W—X—Y—Z
wherein:
W is said signal peptide;
X is said chemokine-binding peptide;
Y is said linker; and
Z is said Fc domain or fragment thereof.