Therapeutic and diagnostic applications based on the role of the CXCR-4 gene in tumorigenesis
View Patent ↗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 Applicant's 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 the proliferation of a cell within a brain tumor, neuroblastoma or breast tumor that over-expresses SDF-1 (SEQ ID NO: 4) in a subject comprising administering to the subject in which such treatment is desired a therapeutically effective amount of an antibody that specifically binds to SDF-1 (SEQ ID NO:4) and that inhibits SDF-1 binding to CXCR-4 on the tumor cell.
2. The method of claim 1 in which the cell that over-expresses SDF-1 (SEQ ID NO: 4) is malignant.
3. The method of claim 1 in which the subject is a human.
4. The method of claim 1 in which the cell that over-expresses SDF-1 (SEQ ID NO: 4) is within the brain tumor selected from meningioma, or malignant glioma and wherein the administration is into the central nervous system.
5. The method of claim 4 in which the glioma is glioblastoma multiforme.
6. The method of claim 1 in which the antibody is a polyclonal antibody or a monoclonal antibody or antigen binding fragment thereof.
7. The method of claim 1 , wherein the antibody is a chimeric antibody, a single chain antibody, a Fab′, a F(ab′) 2 or a Fab fragment.
8. The method of claim 1 , wherein the antibody is a bispecific antibody.
9. The method of claim 1 , wherein the antibody is conjugated with a label or therapeutic moiety.
10. The method of claim 9 , wherein the label or therapeutic moiety is a radioactive metal ion, a toxin, or a drug.