Anti-TAT226 antibodies and immunoconjugates
Anti-TAT226 antibodies and immunoconjugates thereof are provided. Methods of using anti-TAT226 antibodies and immunoconjugates thereof are provided.
1. A method of treating a cell proliferative disorder comprising cells that express TAT226, comprising administering to an individual having said disorder an effective amount of an antibody that binds to TAT226, or antigen-binding fragment thereof, wherein the antibody comprises: a heavy chain variable domain comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO:4, a HVR-H2 comprising the amino acid sequence of SEQ ID NO:5, and a HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:6-10; a light chain variable domain comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO:12, a HVR-L2 comprising the amino acid sequence of SEQ ID NO:13, and a HVR-L3 comprising an amino acid sequence selected from SEQ ID NO:14-18, wherein the antibody or antigen-binding fragment thereof is covalently attached to a cytotoxic agent to form an antibody-drug conjugate.
2. The method of claim 1 , wherein the HVR-H3 comprises the amino acid sequence of SEQ ID NO:9, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:17.
3. The method of claim 1 , wherein HVR-H3 comprises the amino acid sequence of SEQ ID NO:10, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:18.
4. The method of claim 1 , wherein said antibody or antigen-binding fragment thereof further comprises at least one framework selected from a VH subgroup III consensus framework and a VL subgroup I consensus framework.
5. The method of claim 1 , wherein the antibody comprises a heavy chain variable domain comprising an amino acid sequence selected from SEQ ID NO:21-25 and a light chain variable domain comprising an amino acid sequence selected from SEQ ID NO:26-31.
6. The method of claim 5 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:24, and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:29.
7. The method of claim 5 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:25, and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:30.
8. The method of claim 1 , wherein said antibody or antigen-binding fragment thereof is monoclonal.
9. The method of claim 1 , wherein said antigen-binding fragment is selected from the group consisting of Fab, Fab′-SH, Fv, scFv, and (Fabl) 2 fragments.
10. The method of claim 8 , wherein said antibody or antigen-binding fragment thereof is humanized.
11. The method of any one of claims 1 to 7 , wherein the cytotoxic agent is selected from the group consisting of a toxin, a chemotherapeutic agent, an antibiotic, a radioactive isotope, and a nucleolytic enzyme.
12. The method of claim 1 , wherein the cell proliferative disorder is selected from ovarian cancer, uterine cancer, brain tumor, and Wilms' tumor.
13. The method of claim 12 , wherein the cell proliferative disorder is associated with increased expression of TAT226 on the surface of a cell.
14. The method of any one of claims 1 to 7 , wherein the antibody is a bispecific antibody.
15. The method of any one of claims 1 - 7 , wherein the antibody-drug conjugate comprises the formula Ab-(L-D)p, wherein (a) Ab is the antibody that binds to TAT226, or antigen-binding fragment thereof;
(b) L is a linker;
(c) D is a drug; and
(d) p is 1 to about 8.
16. The method of claim 15 , wherein L comprises one or more of 6-maleimidocaproyl (“MC”), maleimidopropanoyl (“MP”), valine-citrulline (“val-cit” or “vc”), alanine-phenylalanine (“ala-phe”), p-aminobenzyloxycarbonyl (a “PAB”), N-Succinimidyl 4-(2-pyridylthio) pentanoate (“SPP”), N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate (“SMCC”), and N-Succinimidyl (4-iodo-acetyl) aminobenzoate (“SIAB”).
17. The method of claim 15 , wherein D comprises one or more of maytansinoid, auristatin, and dolastatin.
18. The method of claim 16 , wherein D comprises one or more of maytansinoid, auristatin, and dolastatin.
19. The method of claim 17 , wherein D comprises auristatin and the auristatin is MMAE or MMAF.
20. The method of claim 18 , wherein D comprises auristatin and the auristatin is MMAE or MMAF.