HER3 antibodies and uses thereof
Provided herein are antibodies specific for HER3. Also provided are methods of treating cancer in a subject comprising administering an effective amount of the antibodies described herein to the subject.
1. An antibody specific for HER3, wherein the antibody does not block ligand binding and wherein the antibody blocks phosphorylation of HER3, wherein the antibody comprises a light chain with polypeptide sequences comprising SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5 and a heavy chain with polypeptide sequences comprising SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8.
2. The antibody of claim 1 , wherein the phosphorylation is independent of ligand binding to HER3.
3. The antibody of claim 1 , wherein the antibody at low doses in vitro blocks phosphorylation of HER3 in a cancer cell expressing HER3.
4. The antibody of claim 1 , wherein the antibody sensitizes blocking phosphorylation of HER2 and EGFR.
5. The antibody of claim 1 wherein the light chain comprises SEQ ID NO: 2 and the heavy chain comprises SEQ ID NO: 1.
6. A method of treating cancer in a subject comprising administering to the subject an effective amount of the antibody of claim 1 .
7. The method of claim 6 , wherein the subject is selected as having a HER3 expressing cancer.
8. The method of claim 6 , further comprising administering to the subject an antibody that blocks ligand binding to HER3.
9. The method of claim 6 , further comprising administering to the subject an antibody that blocks ligand binding to HER2.
10. The method of claim 6 , further comprising administering to the subject one or more chemotherapeutic agents.
11. The method of claim 6 , further comprising administering to the subject an antibody that blocks ligand binding to EGFR.
12. The method of claim 6 , further comprising administering to the subject one or more tyrosine kinase inhibitors.
13. The method of claim 12 , wherein the one or more tyrosine kinase inhibitors are selected from the group consisting of Erlotinib and Lapatinib.
14. A method of reducing resistance to a tyrosine kinase inhibitor in a subject, comprising administering to the subject the HER3 antibody of claim 1 .
15. The method of claim 14 , further comprising administering to the subject an antibody that blocks HER3 ligand binding.
16. A method of reducing resistance to a chemotherapeutic agent in a subject, comprising administering to the subject the HER3 antibody of claim 1 .
17. The method of claim 16 , further comprising administering to the subject an antibody that blocks HER3 ligand binding.