Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof
Disclosed herein are isolated human monoclonal antibodies, and functional fragments thereof, that specifically bind HMW-MAA. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect HMW-MAA in a sample. Methods of diagnosing cancer, or confirming a diagnosis of cancer, are disclosed herein that utilize these antibodies. Methods of treating a subject with cancer are also disclosed.
1. A method of treating a subject having a cancer that expresses HMW-MAA, comprising administering to the subject a therapeutically effective amount of a HMW-MAA-specific human monoclonal antibody or antigen-binding fragment thereof, wherein the heavy chain variable region of the antibody or antigen-binding fragment thereof comprises amino acids 27-38, 56-65 and 105-115 of SEQ ID NO: 5, and the light chain variable region of the antibody or antigen-binding fragment thereof comprises amino acids 27-38, 56-65 and 105-110 of SEQ ID NO: 6, thereby treating the subject having the cancer that expresses HMW-MAA wherein the antigen-binding fragment thereof is conjugated to an effector molecule.
2. The method of claim 1 , wherein the heavy chain variable region comprises SEQ ID NO: 5.
3. The method of claim 1 , wherein the light chain variable region comprises SEQ ID NO: 6.
4. The method of claim 1 , wherein the heavy chain variable region comprises SEQ ID NO: 5 and the light chain variable region comprises SEQ ID NO: 6.
5. The method of claim 1 , wherein the antigen-binding fragment is a Fab, a Fab′, a F(ab)′ 2 , a single chain Fv (scFv), or a disulfide stabilized Fv (dsFv).
6. The method of claim 5 , wherein the antigen-binding fragment is a scFv.
7. The method of claim 1 , wherein the antibody is an IgG.
8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is conjugate to an effector molecule.
9. The method of claim 1 , wherein the cancer is melanoma, breast cancer, head and neck squamous cell carcinoma, prostate cancer, ovarian cancer, colon cancer, glioma, stomach cancer or pancreatic cancer.
10. A method of detecting cancer or confirming the diagnosis of cancer in a subject, comprising:
contacting a sample from the subject with a HMW-MAA-specific human monoclonal antibody or antigen-binding fragment thereof, wherein the heavy chain variable region of the antibody or antigen-binding fragment thereof comprises amino acids 27-38, 56-65 and 105-115 of SEQ ID NO: 5, and the light chain variable region of the antibody or antigen-binding fragment thereof comprises amino acids 27-38, 56-65 and 105-110 of SEQ ID NO: 6; and
detecting binding of the isolated human monoclonal antibody or antigen-binding fragment thereof to the sample,
wherein an increase in binding of the isolated human monoclonal antibody or antigen-binding fragment thereof to the sample as compared to binding of the isolated human monoclonal antibody or antigen-binding fragment thereof to a control sample detects cancer in the subject or confirms the diagnosis of cancer in the subject.
11. The method of claim 10 , wherein the isolated human monoclonal antibody or antigen-binding fragment thereof is directly labeled.
12. The method of claim 10 , further comprising:
contacting a second antibody that specifically binds the isolated human monoclonal antibody or antigen-binding fragment thereof with the sample, and
detecting the binding of the second antibody,
wherein an increase in binding of the second antibody to the sample as compared to binding of the second antibody to a control sample detects cancer in the subject or confirms the diagnosis of cancer in the subject.
13. The method of claim 10 , wherein the cancer is melanoma, breast cancer, head and neck squamous cell carcinoma, prostate cancer, ovarian cancer, colon cancer, glioma, stomach cancer or pancreatic cancer.