Carbonic anhydrase IX (G250) antibodies and methods of use thereof
The invention provides scFv antibodies and monoclonal antibodies that bind to and decrease an activity of Carbonic Anhydrase IX (G250). Also provided are the methods of treating and/or preventing cancer, such as renal clear cell cancer. Also provided are methods of identifying a carbonic anhydrase IX (G250) protein. The invention additionally provides methods of modifying immune effector cells, and the immune effector cells modified thereby.
1. A method of treating a patient diagnosed with cancer comprising, administering to a patient in need thereof a therapeutically effective amount of an anti-carbonic anhydrase IX (CAIX) antibody or antigen-binding fragment thereof, the antibody or binding fragment comprising:
a. a heavy chain with a CDR1 comprising an amino acid sequence SYAMS (SEQ ID NO: 55);
b. a heavy chain with a CDR2 comprising an amino sequence AISXXGGXTXXADSVKG (SEQ ID NO: 58) or AISGSGGSTTTADSVKG (SEQ ID NO: 59);
c. a heavy chain with a CDR3 comprising an amino sequence NGNYRGAFDI (SEQ ID NO: 65);
d. a light chain with a CDR1 comprising an amino sequence TGSSSNIGAGYDVH (SEQ ID NO: 61);
e. a light chain with a CDR2 comprising an amino sequence GNNNRPS (SEQ ID NO: 62); and
f. a light chain with a CDR3 comprising an amino sequence QSYDSSLSAWVV (SEQ ID NO: 63), and wherein the patient has renal cancer.
2. The method of claim 1 , wherein administration of the antibody or binding fragment reduces carbonic anhydrase activity in the patient.
3. The method of claim 1 , wherein the renal cancer is renal clear cell cancer.
4. The method of claim 1 , wherein the heavy chain CDR2 of the antibody comprises AISGSGGSTTTADSVKG (SEQ ID NO: 59).
5. The method of claim 1 , wherein the antibody or binding fragment is human or humanized.
6. The method of claim 1 , wherein the antibody or binding fragment is chimeric.
7. The method of claim 1 , wherein the antibody or binding fragment is modified to enhance antibody-dependent cellular cytotoxicity.
8. The method of claim 7 , wherein the modification comprises introduction of at least one cysteine residue into a Fe region of the antibody or binding fragment.
9. The method of claim 8 , wherein the antibody or binding fragment is a homodimeric antibody.
10. The method of claim 1 , wherein the antibody or binding fragment is conjugated to a cytotoxic agent.
11. The method of claim 1 further comprising administering a second therapeutic agent to the patient.
12. The method of claim 11 , wherein the second agent comprises a second antibody.
13. The method of claim 12 , wherein the second antibody comprises a different anti-CAIX antibody.
14. The methods of claim 12 , wherein the second antibody is Avastin, Erbitux, Humira, Xolair, Zavalin, Campath, Mylotarg, Herceptin, Remicaide, Simulect, Synagis, Zenapax, Rituxan, Panorex, ReoPro, Oncoscint, or OKT3.
15. The method of claim 11 , wherein the second agent comprises an anti-neoplastic agent.
16. The method of claim 15 , wherein the anti-neoplastic agent comprises a small molecule, a growth factor, or a cytokine.
17. The method of claim 16 , wherein the small molecules is acetazolamide.
18. The method of claim 16 , wherein the growth factor is GM-CSF.
19. The method of claim 16 , wherein the cytokine is IL-2, IL-12, or TNF-α.