Compositions and methods for detecting and treating diseases and conditions related to chemokine receptors

• US 20050074826A1
• Filed: 08/04/2004
• Published: 04/07/2005
• Est. Priority Date: 11/30/2001
• Status: Active Grant

• Current Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Original Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Inventors: Schall, Thomas J., Summers, Bretton, Burns, Jennifer M., Howard, Maureen C., Miao, Zhenhua
• Granted Patent: US 7,871,619 B2
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57411 of cervix
• CPC Class Codes: G01N 33/57415 of breast
• CPC Class Codes: G01N 33/57426 leukemia
• CPC Class Codes: G01N 33/57434 of prostate
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

Ligands of CCX—CKR2 and the biological role of CCX—CKR2 in cancer is described.

Claims

1. A method of identifying an agent that binds to CCX—

CKR2 on a cell, the method comprising,

contacting a plurality of agents to a CCX—

CKR2 polypeptide comprising an extracellular domain at least 95% identical to an extracellular domain of SEQ ID NO;

2, or a SDF1 or I-TAC-binding fragment thereof, and

selecting an agent that competes with I-TAC or SDF1 for binding to the CCX-CKR2 polypeptide or fragment thereof, thereby identifying an agent that binds to CCX-CKR2 on a cell.

2. The method of claim 1, wherein the cell is a cancer cell.

3. The method of claim 1, further comprising testing the selected agent for the ability to bind to, or inhibit growth of, a cell.

4. The method of claim 3, wherein the cell is a cancer cell.

5. The method of claim 1, further comprising testing the selected agent for the ability to alter kidney function.

6. The method of claim 1, further comprising testing the selected agent for the ability to alter brain or neuronal function.

7. The method of claim 1, further comprising testing the selected agent for the ability to change cell adhesion to endothelial cells.

8. The method of claim 1, wherein the agent is less than 1,500 daltons.

9. The method of claim 1, wherein the agent is an antibody.

10. The method of claim 1, wherein the agent is a polypeptide.

11. The method of claim 1, wherein the CCX—

CKR2 polypeptide comprises the sequence displayed in SEQ ID NO;

2.

12. A method for determining the presence or absence of a cancer cell, the method comprising,

contacting a sample comprising a cell with an agent that specifically binds with SEQ ID NO:

2; and

detecting binding of the agent to a polypeptide in the sample, wherein binding of the agent to the sample indicates the presence of a cancer cell.

13. The method of claim 12, wherein the agent is an antibody.

14. The method of claim 12, wherein the agent is less than 1500 daltons.

15. The method of claim 12, wherein the agent is a polypeptide.

16. The method of claim 12, wherein the polypeptide detected is SEQ ID NO:

2

17. The method of claim 12, wherein the sample is from a human.

18. The method of claim 12, wherein the method is used to diagnose cancer in a human.

19. The method of claim 12, wherein the method is used to provide a prognosis of cancer in a human.

20. The method of claim 12, wherein the cancer is selected from the group consisting of cervical cancer, breast cancer, lymphoma, glioblastomas, prostate cancer, and leukemia.

21. The method of claim 12, wherein the cancer is not Kaposi'"'"'s sarcoma, multicentric Castleman'"'"'s disease or AIDS-associated primary effusion lymphoma.

22. The method of claim 12, wherein the antibody competes with SDF1 and I-TAC for binding to SEQ ID NO:

2.

23. A method of providing a diagnosis or prognosis of an individual having cancer, the method comprising detecting the presence or absence of expression of a polynucleotide encoding a CCX—

CKR2 polypeptide in a cell of an individual, wherein the CCX—

CKR2 polypeptide binds I-TAC and/or SDF 1 and the CCX—

CKR2 polypeptide is at least 95% identical to SEQ ID NO;

2, thereby diagnosing a cancer in the individual.

24. The method of claim 23, wherein the CCX—

CKR2 polypeptide is displayed in SEQ ID NO;

2.

25. The method of claim 23, wherein the cancer is selected from the group consisting of cervical cancer, breast cancer, lymphoma, glioblastomas, prostate cancer, and leukemia.

26. The method of claim 23, wherein the cancer is not Kaposi'"'"'s sarcoma, multicentric Castleman'"'"'s disease or AIDS-associated primary effusion lymphoma.

27. An antibody that specifically competes with SDF-1 and I-TAC for binding to SEQ ID NO:

2.

28. The antibody of claim 27, wherein the antibody is a monoclonal antibody.

29. The antibody of claim 27, wherein the antibody is a humanized antibody.

30. A method comprising,

contacting a cell with an agent that specifically binds to SEQ ID NO:

2, wherein the agent competes with SDF-1 and I-TAC for binding to a CCX—

CKR2 polypeptide, and wherein the cell expresses a CCX—

CKR2 polypeptide comprising an extracellular domain at least 95% identical to an extracellular domain of SEQ ID NO;

2, thereby binding the agent to the CCX—

CKR2 polypeptide on the cell.

31. The method of claim 30, wherein the agent is less than 1,500 daltons.

32. The method of claim 30, wherein the agent is an antibody.

33. The method of claim 30, wherein the agent is a polypeptide.

34. The method of claim 30, wherein the CCX—

CKR2 polypeptide is as displayed in SEQ ID NO;

2.

35. The method of claim 30, wherein the agent is identified by a method comprising

contacting a plurality of agents to a CCX—

CKR2 polypeptide comprising an extracellular domain at least 95% identical to an extracellular domain of SEQ ID NO;

2, or a SDF1 or I-TAC-binding fragment thereof; and

selecting an agent that competes with I-TAC or SDF-1 for binding to the CCX—

CKR2 polypeptide or fragment thereof, thereby identifying an agent that binds to a cancer cell.

36. A method of treating cancer in an individual, the method comprising administering to the individual a therapeutically effective amount of a polynucleotide that inhibits expression of a CCX—

CKR2 polynucleotide.

37. The method of claim 36, wherein the CCX—

CKR2 polynucleotide encodes SEQ ID NO;

2.

38. The method of claim 36, wherein the CCX—

CKR2 polynucleotide comprises SEQ ID NO;

1.

39. A method of treating cancer in an individual, the method comprising administering to the individual a therapeutically effective amount of an agent that competes with SDF1 and I-TAC for binding to SEQ ID NO:

2.

40. The method of claim 39, wherein the agent is less than 1,500 daltons.

41. The method of claim 39, wherein the agent is an antibody.

42. The method of claim 39, wherein the agent is a polypeptide.

43. The method of claim 39, wherein the agent is identified by a method comprising

contacting a plurality of agents to a CCX—

CKR2 polypeptide comprising an extracellular domain at least 95% identical to an extracellular domain of SEQ ID NO;

2, or a SDF1 or I-TAC-binding fragment thereof; and

selecting an agent that competes with I-TAC or SDF-1 for binding to the CCX—

CKR2 polypeptide or fragment thereof, thereby identifying an agent that binds to a cancer cell.

44. The method of claim 39, wherein the cancer is selected from the group consisting of cervical cancer, breast cancer, lymphoma, glioblastomas, prostate cancer, and leukemia.

45. The method of claim 39, wherein the cancer is not Kaposi'"'"'s sarcoma, multicentric Castleman'"'"'s disease or AIDS-associated primary effusion lymphoma.