Monoclonal antibodies to human 14-3-3 epsilon and human 14-3-3 epsilon sv
The present invention provides isolated antibodies that bind to 14-3-3 epsilon that are useful in the recognition of tumor cells and tumor specific delivery of drugs and therapies.
1. An isolated antibody, wherein the antibody specifically binds 14-3-3 epsilon and the heavy chain comprises the amino acid-sequences of SEQ ID NOs: 8, 9, and 10, and the light chain comprises the amino acid-sequences of SEQ ID NOs: 5, 6, and 7.
2. The isolated antibody of claim 1 , wherein the antibody is encoded by a nucleic acid sequence comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2.
3. The isolated antibody of claim 1 , wherein the antibody specifically binds to an epitope selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15.
4. The isolated antibody of claim 1 , wherein the antibody is selected from the group consisting of a single-chain antibody, an antibody fragment, a chimeric antibody, or a humanized antibody.
5. The isolated antibody of claim 1 , wherein the antibody is conjugated directly or indirectly to a payload selected from the group consisting of a detectable label, a therapeutic agent, or a combination thereof.
6. The isolated antibody of claim 1 , wherein the antibody is conjugated directly or indirectly to a nanoparticle or a liposome.
7. The isolated antibody of claim 5 , wherein the detectable label and/or therapeutic agent is a radionuclide.
8. A method of detecting a tumor in a subject, the method comprising:
a) exposing a target area of the subject where the presence of a tumor is suspected to ionizing radiation;
b) administering to the subject a composition to detect the presence of 14-3-3 epsilon in the target area, wherein the composition comprises one or more targeting antibodies of claim 1 , wherein each targeting antibody specifically binds to 14-3-3 epsilon exposed on an irradiated cell and is conjugated to a detectable label; and
c) detecting the detectable label to detect the presence of 14-3-3 epsilon, wherein the presence of 14-3-3 epsilon indicates the presence of a tumor in the target area of the subject.
9. The method of claim 8 , wherein the exposing comprises exposing the tumor to at least about 2 Gy ionizing radiation.
10. The method of claim 8 , wherein the administering comprises administering the antibody 0 hours to about 24 hours following radiation exposure.
11. The method of claim 8 , wherein the detectable label is a radionuclide.
12. The method of claim 11 , wherein the detecting comprises detecting the radionuclide label using positron emission tomography, single photon emission computed tomography, gamma camera imaging, or rectilinear scanning.
13. The method of claim 8 , wherein the tumor is a lung carcinoma.
14. A method of enhancing radiotherapy in a subject, the method comprising administering to the subject a pharmacologically effective amount of the isolated anti-14-3-3 epsilon antibody of claim 1 , wherein the isolated anti-14-3-3 epsilon antibody is conjugated to a therapeutic agent, such that radiotherapy is enhanced.
15. The method of claim 14 , wherein the subject has cancer.
16. The method of claim 15 , wherein the cancer is lung carcinoma.
17. The method of claim 14 , wherein the administering comprises administering the antibody subsequent to radiation exposure.