Methods and compositions for modulating tumor cell activity
View Patent ↗Antibodies which target clusterin, a protein involved in the epithelial-to-mesenchymal transition of carcinoma cells, are identified and characterized. The antibodies may be used to modulate tumour cell activity through binding to clusterin.
1. An isolated antibody which specifically binds to an epitope of clusterin located between amino acids 421 and 443 selected from the group consisting of:
a) an antibody comprising three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:8 and three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:20;
b) an antibody comprising three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:9 and three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:20,
c) an antibody comprising three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:10 and three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:21;
d) an antibody comprising three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.11 and three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO. :22; and
e) an antibody comprising three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:12 and three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:23.
2. The antibody of claim 1 , wherein said antibody comprises the three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:8 and the three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:20.
3. The antibody of claim 1 , wherein said antibody comprises the three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:9 and the three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:20.
4. The antibody of claim 1 , wherein said antibody comprises the three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.: 10 and the three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:21.
5. The antibody of claim 1 , wherein said antibody comprises the three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.:11 and the three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:22.
6. The antibody of claim 1 , wherein said antibody comprises the three complementarity-determining regions of a light chain variable region set forth in SEQ ID NO.: 12 and the three complementarity-determining regions of a heavy chain variable region set forth in SEQ ID NO.:23.
7. A composition comprising the antibody of claim 1 and a pharmaceutically suitable carrier.
8. The antibody or antigen binding fragment of claim 1 , wherein said antibody is monoclonal.
9. An isolated antibody which specifically binds to an epitope of clusterin located between amino acids 421 and 443 and which comprises:
a) a light chain variable region as set forth in SEQ ID NO.: 8 and a heavy chain variable region as set forth in SEQ ID NO.:20;
b) a light chain variable region as set forth in SEQ ID NO.:9 and a heavy chain variable region as set forth in SEQ ID NO.:20;
c) a light chain variable region as set forth in SEQ ID NO.: 10 and a heavy chain variable region as set forth in SEQ ID NO.:21;
d) a light chain variable region as set forth in SEQ ID NO.: 11 and a heavy chain variable region as set forth in SEQ ID NO.: 22, or
e) a light chain variable region as set forth in SEQ ID NO.: 12 and a heavy chain variable region as set forth in SEQ ID NO.:23.
10. The antibody of claim 9 , wherein said antibody comprises a light chain variable region as set forth in SEQ ID NO.: 11 and a heavy chain variable region as set forth in SEQ ID NO.: 22.
11. The antibody of claim 9 , wherein said antibody comprises a light chain variable region as set forth in SEQ ID NO.: 12 and a heavy chain variable region as set forth in SEQ ID NO.:23.
12. A composition comprising the antibody of claim 9 and a pharmaceutically suitable carrier.
13. The antibody or antigen binding fragment of claim 9 , wherein said antibody is monoclonal.
14. A composition comprising the antibody of claim 10 and a pharmaceutically suitable carrier.
15. The antibody or antigen binding fragment of claim 10 , wherein said antibody is monoclonal.
16. A composition comprising the antibody of claim 11 and a pharmaceutically suitable carrier.
17. The antibody or antigen binding fragment of claim 11 , wherein said antibody is monoclonal.
18. The composition of claim 7 , wherein said antibody is monoclonal.
19. The composition of claim 12 , wherein said antibody is monoclonal.
20. The composition of claim 14 , wherein said antibody is monoclonal.
21. The composition of claim 16 , wherein said antibody is monoclonal.
22. A method for inhibiting epithelial-to-mesenchymal transition in carcinoma cells, the method comprising administering the antibody of claim 1 to a mammal in need.
23. A method for inhibiting epithelial-to-mesenchymal transition in carcinoma cells, the method comprising administering the antibody of claim 9 to a mammal in need.
24. A method for inhibiting epithelial-to-mesenchymal transition in carcinoma cells, the method comprising administering the antibody of claim 10 to a mammal in need.
25. A method for inhibiting epithelial-to-mesenchymal transition in carcinoma cells, the method comprising administering the antibody of claim 11 to a mammal in need.
26. The method of claim 22 , wherein said antibody is monoclonal.
27. The method of claim 23 , wherein said antibody is monoclonal.
28. The method of claim 24 , wherein said antibody is monoclonal.
29. The method of claim 25 , wherein said antibody is monoclonal.