Therapeutic and diagnostic applications based on the role of the CXCR-4 gene in tumorigenesis
The present invention relates to the identification of a novel role of CXCR-4 in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of CXCR-4 in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for CXCR-4. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of CXCR-4 gene expression or the inhibition of CXCR-4 activity in transformed cells reverses the transformed phenotype.
1. A method of inhibiting proliferation of a cell within a tumor that over-expresses CXCR-4 (SEQ ID NO: 2) in a subject comprising administering to the subject an effective amount of an antibody specific for CXCR-4 (SEQ ID NO:2).
2. The method according to claim 1 in which the cell that over-expresses CXCR-4 (SEQ ID NO:2) is malignant.
3. The method according to claim 1 in which the cell that over-expresses CXCR-4 (SEQ ID NO:2) is within the tumor that comprises a cancer selected from the group consisting of brain cancer, breast cancer, colon cancer, prostate cancer and B cell lymphoma.
4. The method according to claim 1 in which the subject is a human.
5. The method according to claim 3 in which the brain cancer is selected from the group consisting of glioblastoma, glioma, meningioma, astrocytoma, medulloblastoma, neuroectodermal cancer and neuroblastoma.
6. The method according to claim 5 in which the glioblastoma is glioblastoma multiforme.
7. The method according to claim 1 in which the cells that over-express CXCR-4 (SEQ ID NO:2) are associated with hyperproliferative disorders or malignant disorders—has been inserted after the phase “are associated with”.
8. The method according to claim 1 in which the antibody is a polyclonal or a monoclonal antibody or antigen binding fragment thereof.
9. The method according to claim 1 , wherein the antibody is a chimeric antibody, a single chain antibody, a Fab′, a F(ab′) 2 , or a Fab fragment.
10. The method according to claim 1 , wherein the antibody is a bispecific antibody.
11. The method according to claim 1 , wherein the antibody is conjugated with a label or therapeutic moiety.
12. The method according to claim 11 , wherein the label or therapeutic moiety is a radioactive metal ion, a toxin, or a drug.
13. A method comprising administering to a subject detected to have cells that over-express CXCR-4, an effective amount of an antibody specific for CXCR-4 (SEQ ID NO:2) to prevent proliferation of the cells over-expressing CXCR-4 (SEQ ID NO:2).
14. A method for killing a cell that expresses an increased level of CXCR-4 (SEQ ID NO:2) by administering an effective amount of an antibody specific for CXCR-4.
15. The method according to claim 14 , wherein the antibody is a polyclonal or a monoclonal antibody or an antigen binding fragment thereof.
16. The method according to claim 14 , wherein the antibody is a chimeric antibody, a single chain antibody; a Fab′, a F(ab′) 2 , or a Fab fragment.
17. The method according to claim 14 , wherein the antibody is a bispecific antibody.
18. The method according to claim 14 , wherein the antibody is conjugated with a label or therapeutic moiety.
19. The method according to claim 18 , wherein the label or therapeutic moiety is a radioactive metal ion, a toxin, or a drug.