Antibodies recognizing a carbohydrate containing epitope on CD-43 and CEA expressed on cancer cells and methods using same
The present invention provides antibodies (such as chimeric and humanized antibodies) specifically bind to an epitope on CD43 and CEA expressed on nonhematopoietic cancer cells. In addition, the present invention also provides use of the antibodies described herein for diagnostic and therapeutic purposes.
1. A method for treating nonhematopoietic cancer in an individual having cancer comprising administering to the individual an effective amount of a composition comprising a humanized antibody, wherein the antibody specifically binds to a carbohydrate epitope on a CD43 or a carcinoembryonic antigen (CEA) expressed by the nonhematopoietic cancer cells in the individual, wherein the antibody comprises a heavy chain and a light chain, wherein
(a) the heavy chain comprises a heavy chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:1, and a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:9, wherein the hinge region of the heavy chain constant region comprises at least one amino acid insertion, deletion or substitution; and
(b) the light chain comprises a light chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:2, and a light chain constant region comprising the amino acid sequence of SEQ ID NO:10 and further comprising at least one amino acid insertion in the constant region,
wherein the nonhematopoietic cancer is colorectal, pancreatic, or gastric cancer.
2. The method of claim 1 , wherein the antibody is conjugated to a cytotoxin.
3. A method for treating nonhematopoietic cancer in an individual having cancer comprising administering to the individual an effective amount of a composition comprising an antibody, wherein the antibody specifically binds to a carbohydrate epitope on a CD43 or a carcinoembryonic antigen (CEA) expressed by the nonhematopoietic cancer cells in the individual, wherein the antibody comprises a heavy chain and a light chain, wherein
(a) the heavy chain comprises a heavy chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:1, and a heavy chain constant region comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:11-30, and
(b) the light chain comprises a light chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:2, and a light chain constant region comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:10 and 31-37,
wherein the nonhematopoietic cancer is colorectal, pancreatic, or gastric cancer.
4. The method of claim 3 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:27.
5. The method of claim 3 , wherein the heavy chain variable region comprises the amino acid sequence of residues 20-137 of SEQ ID NO:1 and the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:27, and the light chain variable region comprises the amino acid sequence of residues 20-131 of SEQ ID NO:2 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:10.
6. The method of claim 3 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29.
7. The method of claim 3 , wherein the heavy chain variable region comprises the amino acid sequence of residues 20-137 of SEQ ID NO:1 and the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence of residues 20-131 of SEQ ID NO:2 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:34.
8. The method of claim 3 , wherein the heavy chain variable region comprises the amino acid sequence of residues 20-137 of SEQ ID NO:1 and the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence of residues 20-131 of SEQ ID NO:2 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:35.
9. The method of claim 3 , wherein the antibody is a humanized antibody.
10. The method of claim 9 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:27, and the light chain constant region comprises the amino acid sequence of SEQ ID NO:10.
11. The method of claim 9 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29, and the light chain constant region comprises the amino acid sequence of SEQ ID NO:34.
12. The method of claim 9 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29, and the light chain constant region comprises the amino acid sequence of SEQ ID NO:35.
13. The method of claim 3 , wherein the antibody is a chimeric antibody.
14. The method of claim 3 , wherein the antibody is conjugated to a cytotoxin.
15. A method for treating nonhematopoietic cancer in an individual comprising administering to the individual an amount of a humanized antibody and an amount of another anti-cancer agent, wherein the antibody specifically binds to a carbohydrate epitope on a CD43 or a carcinoembryonic antigen (CEA) expressed by the nonhematopoietic cancer cells in the individual, wherein the antibody comprises a heavy chain and a light chain, wherein
(a) the heavy chain comprises a heavy chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:1, and a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:9, wherein the hinge region of the heavy chain constant region comprises at least one amino acid insertion, deletion or substitution; and
(b) the light chain comprises a light chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:2, and a light chain constant region comprising the amino acid sequence of SEQ ID NO:10 and further comprising at least one amino acid insertion in the constant region,
whereby the antibody and the anti-cancer agent in conjunction provides effective treatment of cancer in the individual, wherein the nonhematopoietic cancer is colorectal, pancreatic, or gastric cancer.
16. The method of claim 15 , wherein the anti-cancer agent is a chemotherapeutic agent.
17. A method for treating nonhematopoietic cancer in an individual comprising administering to the individual an amount of an antibody and an amount of another anti-cancer agent, wherein the antibody specifically binds to a carbohydrate epitope on a CD43 or a carcinoembryonic antigen (CEA) expressed by the nonhematopoietic cancer cells in the individual, wherein the antibody comprises a heavy chain and a light chain, wherein
(a) the heavy chain comprises a heavy chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:1, and a heavy chain constant region comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:11-30, and
(b) the light chain comprises a light chain variable region comprising the three complementarity determining regions (CDRs) from the amino acid sequence of SEQ ID NO:2, and a light chain constant region comprising the amino acid sequence selected from the group consisting of SEQ ID NOS:10 and 31-37,
whereby the antibody and the anti-cancer agent in conjunction provides effective treatment of cancer in the individual, wherein the nonhematopoietic cancer is colorectal, pancreatic, or gastric cancer.
18. The method of claim 17 , wherein the anti-cancer agent is a chemotherapeutic agent.
19. The method of claim 17 , wherein the heavy chain variable region comprises the amino acid sequence of residues 20-137 of SEQ ID NO:1 and the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:27, and the light chain variable region comprises the amino acid sequence of residues 20-131 of SEQ ID NO:2 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:10.
20. The method of claim 17 , wherein the heavy chain variable region comprises the amino acid sequence of residues 20-137 of SEQ ID NO:1 and the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence of residues 20-131 of SEQ ID NO:2 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:34.
21. The method of claim 17 , wherein the heavy chain variable region comprises the amino acid sequence of residues 20-137 of SEQ ID NO:1 and the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence of residues 20-131 of SEQ ID NO:2 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:35.
22. The method of claim 1 , wherein the light chain constant region comprises the amino acid sequence selected from the group consisting of SEQ ID NOS:31-37.
23. The method of claim 1 , wherein the heavy chain constant region comprises the amino acid sequence selected from the group consisting of SEQ ID NOS:11-30.
24. The method of claim 1 , wherein the heavy chain constant region comprises the amino acid sequence selected from the group consisting of SEQ ID NOS:25-30.
25. The method of claim 3 , wherein the antibody is conjugated to a cytotoxic agent.
26. The method of claim 25 , wherein the cytotoxic agent is a radioisotope or a toxin.
27. The method of claim 17 , wherein the antibody is conjugated to a cytotoxic agent.
28. The method of claim 27 , wherein the cytotoxic agent is a radioisotope or a toxin.
29. The method of claim 3 , wherein the cancer is colorectal cancer.
30. The method of claim 3 , wherein the cancer is pancreatic cancer.
31. The method of claim 3 , wherein the cancer is gastric cancer.
32. The method of claim 17 , wherein the cancer is colorectal cancer.
33. The method of claim 17 , wherein the cancer is pancreatic cancer.
34. The method of claim 17 , wherein the cancer is gastric cancer.