Compositions and methods for treating HIF-1α over-expressing cancers
Described herein are compositions that include monoclonal antibodies that specifically bind Hsp90α and methods of using the same to treat HIF-1α-overexpressing cancer. In some embodiments, the cancers are breast cancer or lung cancer. The monoclonal antibodies bind the epitope TKPIWTRNP (SEQ ID NO: 1) in Hsp90α or VKHFSVEGQ (SEQ ID NO: 2) in Hsp90α.
1. A method for treating or preventing metastasis of HIF-1α-overexpressing cancer in a subject in need thereof comprising:
administering a therapeutically effective amount of a composition comprising an inhibitor of Hsp90α to the subject,
wherein the inhibitor of Hsp90α is a monoclonal antibody or a fragment thereof which binds TKPIWTRNP (SEQ ID NO: 1) epitope of Hsp90α or a monoclonal antibody or a fragment thereof which binds VKHFSVEGQ (SEQ ID NO: 2) epitope of Hsp90α, wherein the monoclonal antibody is selected from the group consisting of: a monoclonal antibody produced by hybridoma 1G6-D7, ATCC accession number PTA-125207 and a monoclonal antibody produced by hybridoma 5C4-D4, ATCC accession number PTA-125208,
so as to treat or prevent metastasis of HIF-1α-overexpressing cancer in the subject.
2. The method of claim 1 , wherein the cancer is breast cancer.
3. The method of claim 1 , wherein the cancer is lung cancer.
4. The method of claim 1 , wherein the inhibitor further targets amino acids Lys-270, Lys-277 or a combination thereof of Hsp90α.
5. The method of claim 1 , wherein the inhibitor of Hsp90α is administered intravenously, intramuscularly, intraperitoneally, orally or via inhalation.
6. The method of claim 1 , wherein the effective amount of the inhibitor of Hsp90α or fragments thereof is about 1-5 mg/kg/day, 5-10 mg/kg/day, 10-50 mg/kg/day, or 10-30 mg/kg/day.
7. The method of claim 1 , further comprising administering additional cancer therapy to the subject, wherein the additional therapy is selected from chemotherapy, immunotherapy, radiation therapy or a combination thereof.
8. The method of claim 7 , wherein the monoclonal antibody, or a fragment thereof, and the additional therapy are administered sequentially.
9. The method of claim 7 , wherein the monoclonal antibody, or a fragment thereof, and the additional therapy are administered simultaneously.
10. The method of claim 1 , wherein the therapeutically effective amount of the monoclonal antibody or a fragment thereof is 0.01 to 0.05 μg/kg/day, 0.05-0.1 μg/kg/day, 0.1 to 0.5 μg/kg/day, 0.5 to 5 μg/kg/day, 5 to 10 μg/kg/day, 10 to 20 μg/kg/day, 20 to 50 μg/kg/day, 50 to 100 μg/kg/day, 100 to 150 μg/kg/day, 150 to 200 μg/kg/day, 200 to 250 μg/kg/day, 250 to 300 μg/kg/day, 300 to 350 μg/kg/day, 350 to 400 μg/kg/day, 400 to 500 μg/kg/day, 500 to 600 μg/kg/day, 600 to 700 μg/kg/day, 700 to 800 μg/kg/day, 800 to 900 μg/kg/day, 900 to 1000 μg/kg/day or a combination thereof.
11. The method of claim 1 , wherein the therapeutically effective amount of the monoclonal antibody or a fragment thereof is 0.01 to 0.05 mg/kg/day, 0.05-0.1 mg/kg/day, 0.1 to 0.5 mg/kg/day, 0.5 to 1 mg/kg/day, 1 to 5 mg/kg/day, 5 to 10 mg/kg/day, 10 to 15 mg/kg/day, 15 to 20 mg/kg/day, 20 to 50 mg/kg/day, 50 to 100 mg/kg/day, 100 to 200 mg/kg/day, 200 to 300 mg/kg/day, 300 to 400 mg/kg/day, 400 to 500 mg/kg/day, 500 to 600 mg/kg/day, 600 to 700 mg/kg/day, 700 to 800 mg/kg/day, 800 to 900 mg/kg/day, 900 to 1000 mg/kg/day or a combination thereof.
12. The method of claim 1 , wherein the monoclonal antibody or a fragment thereof is administered once a day (SID/QD), twice a day (BID), three times a day (TID), four times a day (QID), or more.