HER3 inhibitor for modulating radiosensitivity
The present invention relates to the use of an inhibitor of HER-3 for the treatment of a hyperproliferative disease in combination with radiation treatment.
1. A method of treating a hyperproliferative disease in a subject comprising administering to the subject an anti-HER-3 antibody or an antigen-binding fragment thereof in combination with radiation treatment,
wherein the radiation treatment comprises X-ray radiation,
wherein the anti-HER-3 antibody or an antigen-binding fragment thereof comprises a heavy chain variable region with an amino acid sequence comprising SEQ ID NO:70 and a light chain variable region with an amino acid sequence comprising SEQ ID NO:72,
wherein the hyperproliferative disease is head and neck cancer, and
wherein the anti-HER-3 antibody or antigen-binding fragment thereof is administered before the X-ray radiation and sensitizes the head and neck cancer to the X-ray radiation.
2. The method of claim 1 , wherein the anti-HER-3 antibody is a monoclonal antibody, a recombinant antibody, a human antibody, a multispecific antibody, or an antigen-binding fragment thereof.
3. The method of claim 1 , wherein said antigen-binding fragment of the anti-HER-3 antibody is a Fab fragment, a Fab′ fragment, a F(ab′) 2 fragment, a Fv fragment, a diabody, or a single chain antibody molecule.
4. The method of claim 1 , wherein said anti-HER-3 antibody is coupled to an effector group and/or labelling group.
5. The method of claim 4 , wherein said effector group is a radioisotope, a radionuclide, a toxin, a therapeutic group, and/or a chemotherapeutic group.
6. The method of claim 4 , wherein said labelling group is a radioisotope or radionuclide, a fluorescent group, an enzymatic group, a chemiluminescent group, a biotinyl group, or a predetermined polypeptide epitope.
7. The method of claim 1 , wherein the head and neck cancer is head and neck squamous cell carcinoma.
8. The method of claim 1 , wherein the radiation treatment further comprises brachytherapy, radioisotope therapy, or external beam radiation therapy other than X-ray radiation treatment.
9. The method of claim 1 , wherein the radiation treatment is based on a single dose or fractioned dosing of radiation.
10. The method of claim 1 , wherein the method comprises administering a further active compound.
11. The method of claim 10 , wherein the further active compound comprises a chemotherapeutic compound.
12. The method of claim 1 wherein the anti-HER-3 antibody or antigen-binding fragment thereof is administered 4 hours or 48 hours before the X-ray radiation.
13. The method of claim 12 wherein the X-ray radiation is 10 Gy or 16 Gy.
14. The method of claim 13 wherein the X-ray radiation is fractionated.
15. The method of claim 13 wherein the X-ray radiation is a single dose.
16. A method of treating head and neck cancer in a subject, the method comprising:
administering to the subject an anti-HER-3 antibody or an antigen-binding fragment thereof, wherein the anti-HER-3 antibody or an antigen-binding fragment thereof comprises a heavy chain variable region with an amino acid sequence comprising SEQ ID NO:70 and a light chain variable region with an amino acid sequence comprising SEQ ID NO:72, and
subsequently administering to the subject a radiation treatment, the radiation treatment comprising X ray radiation, wherein the anti-HER-3 antibody or antigen-binding fragment thereof sensitizes the head and neck cancer to the X-ray radiation.
17. The method of claim 16 wherein the anti-HER3 antibody or antigen-binding fragment thereof is administered to the subject 4 hours or 48 hours prior to the X-ray radiation.
18. The method of claim 17 wherein the X-ray radiation is 10 Gy or 16 Gy.
19. The method of claim 18 wherein the X-ray radiation is fractionated.
20. The method of claim 18 wherein the X-ray radiation is a single dose.
21. The method of claim 16 wherein the head and neck cancer is head and neck squamous cell carcinoma.