Antibodies directed to monocyte chemo-attractant protein-1 (MCP-1) and uses thereof
Embodiments of the invention described herein relate to antibodies directed to the antigen monocyte chemo-attractant protein-1 (MCP-1) and uses of such antibodies. In particular, in accordance with some embodiments, there are provided fully human monoclonal antibodies directed to the antigen MCP-1. Nucelotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDRs), specifically from FR1 through FR4 or CDR1 through CDR3, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.
1. An isolated human monoclonal antibody that binds to MCP-1 and comprises a heavy chain polypeptide having the sequence of SEQ ID NO.: 62.
2. The antibody of claim 1 , further comprising a light chain polypeptide having the sequence of SEQ ID NO.:64.
3. An isolated antibody immobilized on an insoluble matrix, wherein the antibody is the antibody of claim 1 .
4. A method for assaying the level of monocyte chemo-attractant protein (MCP-1) in a patient sample, comprising:
contacting the anti-MCP-1 antibody of claim 1 with the patient sample; and
detecting the level of MCP-1 in the patient sample.
5. A method according to claim 4 , wherein the patient sample is blood.
6. A composition, comprising the antibody of claim 1 , and a pharmaceutically acceptable carrier.
7. A method of treating a neoplastic disease, comprising:
selecting an animal in need of treatment for a neoplastic disease; and
administering to said animal a therapeutically effective dose of the antibody of claim 1 .
8. The method of claim 7 , wherein said neoplastic disease is selected form the group consisting of: breast cancer, ovarian cancer, bladder cancer, lung cancer, glioblastoma, stomach cancer, endometrial cancer, kidney cancer, colon cancer, pancreatic cancer, and prostate cancer.
9. An isolated human monoclonal antibody that binds to the sequence ISVQRLASYRRITSSK (SEQ ID NO.: 150).
10. A method of manufacturing the antibody of claim 1 , comprising:
immunizing a mammal with a synthetic peptide of MCP-1;
recovering a lymphatic cell that expresses the antibody of claim 1 from the immunized mammal; and
fusing the lymphatic cell with a myeloid-type cell to prepare a hybridoma cell that produces the antibody of claim 1 .
11. The antibody of claim 1 , wherein said antibody is conjugated to a therapeutic agent.
12. The antibody of claim 11 , wherein said therapeutic agent is a toxin.
13. The antibody of claim 12 , wherein said toxin is an immunotoxin.
14. The antibody of claim 11 , wherein said therapeutic agent is a chemotherapeutic agent.
15. The antibody of claim 14 , wherein said chemotherapeutic agent is selected from the group consisting of taxol, doxorubicin, cis-platinum, and 5-fluorouracil.
16. The antibody of claim 11 , wherein said therapeutic agent is a steroid.
17. The antibody of claim 11 , wherein said therapeutic agent is a radioisotope.
18. The antibody of claim 17 , wherein said radioisotope is selected from the group consisting of 3 H, 14 C, 15 N, 35 S, 90 Y, 99 Tc, 111 In, 125 In, and 131 I.
19. The antibody of laim 9 , wherein said antibody is conjugated to a therapeutic agent.
20. The antibody of claim 19 , wherein said therapeutic agent is a toxin.
21. The antibody of claim 20 , wherein said toxin is an immunotoxin.
22. The antibody of claim 20 , wherein said therapeutic agent is a chemotherapeutic agent.
23. The antibody of claim 22 , wherein said chemotherapeutic agent is selected from the group consisting of taxol, doxorubicin, cis-platinum, and 5-fluorouracil.
24. The antibody of 22 , wherein said therapeutic agent is a steroid.
25. The antibody of claim 22 , wherein said therapeutic agent is a radioisotope.
26. The antibody of claim 25 , wherein said radioisotope is selected from the group consisting of 3 H, 14 C, 15 N, 35 S, 90 Y, 99 Tc, 111 In, 125 In, and 131 I.
27. The antibody of claim 1 , wherein said antibody neutralizes the activity of MCP-1.
28. The antibody of claim 3 , wherein said antibody neutralizes the activity of MCP-1.
29. The antibody of claim 9 , wherein said antibody neutralizes the activity of MCP-1.
30. The antibody of claim 1 , wherein said antibody binds to MCP-1 with a dissociation constant (K D ) of approximately 3.0 pM.
31. The antibody of claim 30 , wherein said dissociation constant is 3.3 pM.
32. The antibody of claim 3 , wherein said antibody binds to MCP-1 with a dissociation constant (K D ) of approximately 3.0 pM.
33. The antibody of claim 32 , wherein said dissociation constant is 3.3 pM.
34. The antibody of claim 9 , wherein said antibody binds to MCP-1 with a dissociation constant (K D ) of approximately 3.0 pM.
35. The antibody of claim 34 , wherein said dissociation constant is 3.3 pM.
36. An isolated human monoclonal antigen binding fragment that binds to MCP-1 and comprises a heavy chain polypeptide having the sequence of SEQ ID NO.: 62.
37. The antigen binding fragment of claimn 36 , further comprising a light chain polypeptide having the sequence of SEQ ID NO.: 64.
38. The antigen binding fragment of claim 36 , wherein said binding fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2 , and F v .
39. The antigen binding fragment of claim 36 , wherein said fragment is conjugated to a therapeutic agent.