Methods and compositions for the treatment and diagnosis of endothelial cell disorders and angiogenic disorders
View Patent ↗The invention features methods and compositions for treating and preventing angiogenic disorders and endothelial cells disorders using HspA12B antagonist and HspA12B agonist compounds, respectively.
1. A method of treating cancer in a subject, said method comprising administering to said subject a therapeutically effective amount of an HspA12B-specific antibody, or antibody fragment thereof, in an amount and for a time sufficient to treat or prevent said angiogenic disorder in said subject wherein said HspA12B-specific antibody or antibody fragment thereof is not cytotoxic, and wherein said HspA12B-specific antibody, or antibody fragment thereof, inhibits the biological activity of an HspA12B protein.
2. The method of claim 1 , wherein said biological activity is ATPase activity, heat shock protein or chaperone activity, substrate binding, HspA12B-mediated phosphorylation of Akt, HspA 12B-mediated activation of nitric oxide biological activity or expression levels.
3. The method of claim 1 , wherein said HspA12B-specific antibody, or antibody fragment thereof specifically binds the ATP binding domain or the substrate-binding domain of HspA12B.
4. The method of claim 1 , wherein said cancer is characterized by excessive proliferation, migration, or excess survival of endothelial cells.
5. The method of claim 1 , wherein said HspA12B-specific antibody, or antibody fragment thereof, specifically binds to an epitope consisting of CVDVSTNRSVRAAIDFLSN (SEQ ID NO: 19).
6. A method of treating cancer in a subject, said method comprising administering to said subject a therapeutically effective amount of an HspA12B-specific antibody, or antibody fragment thereof, in an amount and for a time sufficient to treat said cancer in said subject, wherein said HspA12B-specific antibody or antibody fragment thereof specifically binds to an epitope consisting of CVDVSTNRSVRAAIDFLSN (SEQ ID NO: 19).
7. The method of claim 6 , wherein said HspA 12B-specific antibody, or antibody fragment thereof, inhibits the biological activity of an HspA12B protein.
8. The method of claim 7 , wherein said biological activity is ATPase activity, heat shock protein or chaperone activity, substrate binding, HspA12B-mediated phosphorylation of Akt, HspA12B-mediated activation of nitric oxide biological activity or expression levels.
9. The method of claim 6 , wherein said cancer is characterized by excessive proliferation, migration, or excess survival of endothelial cells.