Antibodies against the MUC1-C/extracellular domain (MUC1-C/ECD)
The present invention is directed to antibodies binding to MUC1-C/extracellular domain (MUC1-C/ECD) and methods of using such antibodies to treat cancers that express the MUC1 antigen.
1. An antibody that binds selectively to MUC1-C extracellular domain (MUC1-C/ECD) defined by SEQ ID NO: 2, wherein said antibody comprises a variable region of a heavy chain comprising CDR1, CDR2 and CDR3 regions having SEQ ID NOS: 76, 77 and 78, and a variable region of a light chain comprising CDR1, CDR2 and CDR3 regions having SEQ ID NOS: 79, 80 and 81, respectively.
2. The antibody of claim 1 , wherein said antibody is a single chain antibody or a chimeric antibody.
3. The antibody of claim 1 , wherein said antibody a Fab fragment.
4. The antibody of claim 1 , wherein said antibody is a recombinant antibody having specificity for the MUC1-C/ECD and a distinct cancer cell surface antigen.
5. The antibody of claim 1 , wherein said antibody is a murine antibody.
6. The antibody of claim 5 , wherein said murine antibody is an IgG.
7. The antibody of claim 1 , wherein antibody is a humanized antibody.
8. The antibody of claim 7 , wherein said humanized antibody is an IgG.
9. The antibody of claim 1 , wherein said antibody further comprises a label.
10. The antibody of claim 9 , wherein said label is a peptide tag, an enzyme, a magnetic particle, a chromophore, a fluorescent molecule, a chemiluminescent molecule, or a dye.
11. The antibody of claim 1 , wherein said antibody further comprises an antitumor drug linked thereto.
12. The antibody of claim 11 , wherein said antitumor drug is linked to said antibody through a photolabile linker or through an enzymatically cleaved linker.
13. The antibody of claim 11 , wherein said antitumor drug is a toxin, a radioisotope, a cytokine or an enzyme.
14. The antibody of claim 1 , wherein said antibody is conjugated to a nanoparticle or a liposome.
15. The antibody of claim 1 , wherein the antibody comprises a variable region of a heavy chain having 80% or more homology to SEQ ID NO: 73, and a variable region of a light chain having 80% or more homology to SEQ ID NO: 75.
16. The antibody of claim 1 , wherein said variable regions of heavy and light chains have 85%, 90%, 95% or 99% homology to SEQ ID NO: 73 and 75, respectively.
17. The antibody of claim 1 , wherein the antibody comprises a variable region of a heavy chain encoded by a nucleic acid having 70% or more homology to SEQ ID NO: 72, and a variable region of a light chain encoded by a nucleic acid having 70% or more homology to SEQ ID NO: 74, respectively.
18. The antibody of claim 1 , wherein said variable regions of heavy and light chains are encoded by nucleic acids having 85%, 90%, 95% or 99% homology to SEQ ID NO: 72, and 74, respectively.
19. A fusion protein comprising:
(i) a first single chain antibody that binds selectively to MUC1-C/extracellular domain (ECD) defined by SEQ ID NO: 2, wherein said antibody comprises a variable region of a heavy chain comprising CDR1, CDR2 and CDR3 regions having SEQ ID NOS: 76, 77 and 78, and a variable region of a light chain comprising CDR1, CDR2 and CDR3 regions having SEQ ID NOS: 79, 80 and 81, respectively; and
(ii) a second single chain antibody that binds to a T or B cell.
20. The fusion protein of claim 19 , wherein the first single antibody chain comprises a variable region of a heavy chain having 80% or more homology to SEQ ID NO: 73, and a variable region of a light chain having 80% or more homology to SEQ ID NO: 75, respectively.
21. The fusion protein of claim 19 , wherein the first single antibody chain comprises a variable region of a heavy chain encoded by a nucleic acid having 70% or more homology to SEQ ID NO: 72, and a variable region of a light chain encoded by a nucleic acid having 70% or more homology to SEQ ID NO: 74, respectively.
22. The fusion protein of claim 19 , wherein said second single chain antibody binds to to CD3.
23. The fusion protein of claim 19 , wherein said second single chain antibody binds to a T cell.
24. The fusion protein of claim 19 , wherein said second single chain antibody binds to a B cell.
25. The fusion protein of claim 19 , wherein said fusion protein further comprises a label or a therapeutic moiety.