Antibodies recognizing a carbohydrate containing epitope on CD-43 and CEA expressed on cancer cells and methods using same
The present invention provides novel antibodies specifically bind to an epitope on CD43 and CEA expressed on nonhematopoietic cancer cells, but do not specifically bind to a CD43 expressed by a leukocyte or by a Jurkat cell, and is capable of inducing apoptosis of the nonhematopoietic cancer cell after binding to the epitope on cell surface of the nonhematopoietic cancer cell in the absence of cytotoxin conjugation and immune effector function, wherein the epitope comprises a carbohydrate structure and the binding of the antibody to the epitope is inhibited by a carbohydrate comprising a Le a structure, a Le a -lactose structure, a LNDFH II structure, or a LNT structure. In addition, the present invention also provides use of the antibodies described herein for diagnostic and therapeutic purposes.
1. A method for treating colorectal or gastric cancer in an individual having cancer comprising administering to the individual an effective amount of a composition comprising a monoclonal antibody, wherein the antibody recognizes an epitope on the extracellular surface of a human CD43 expressed by a human colorectal or human gastric cancer cell and comprises a heavy chain variable region comprising the three complementarity determining regions from the amino acid sequence of SEQ ID NO:1, and a light chain variable region comprising the three complementarity determining regions from the amino acid sequence of SEQ ID NO:2.
2. The method of claim 1 , wherein the antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:1, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:2.
3. A method for treating colorectal or gastric cancer in an individual having cancer comprising administering to the individual an effective amount of a composition comprising a monoclonal antibody, wherein the antibody recognizes an epitope on the extracellular surface of a human CD43 expressed by a human colorectal or human gastric cancer cell and comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:7, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:8.
4. A method for treating colorectal or gastric cancer in an individual comprising administering to the individual an amount of a monoclonal antibody and an amount of another anti-cancer agent, whereby the monoclonal antibody and the anti-cancer agent in conjunction provides effective treatment of cancer in the individual, wherein the antibody recognizes an epitope on the extracellular surface of a human CD43 expressed by a human colorectal or human gastric cancer cell and comprises a heavy chain variable region comprising the three complementarity determining regions from the amino acid sequence of SEQ ID NO:1, and a light chain variable region comprising the three complementarity determining regions from the amino acid sequence of SEQ ID NO:2.
5. The method of claim 4 , wherein the antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:1, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:2.
6. A method for treating colorectal or gastric cancer in an individual comprising administering to the individual an amount of a monoclonal antibody and an amount of another anti-cancer agent, whereby the monoclonal antibody and the anti-cancer agent in conjunction provides effective treatment of cancer in the individual, wherein the antibody recognizes an epitope on the extracellular surface of a human CD43 expressed by a human colorectal or human gastric cancer cell and comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:7, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:8.
7. The method of claim 1 , wherein the antibody is conjugated to a cytotoxin.
8. The method of claim 1 , wherein the antibody is a humanized antibody.
9. The method of claim 1 , wherein the individual is a human.
10. The method of claim 4 , wherein the antibody is conjugated to a cytotoxin.
11. The method of claim 4 , wherein the antibody is a humanized antibody.
12. The method of claim 4 , wherein the individual is a human.
13. The method of claim 1 , wherein the antibody is a chimeric antibody.
14. The method of claim 4 , wherein the antibody is a chimeric antibody.
15. The method of claim 7 , wherein the cytotoxin is selected from the group consisting of paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin.
16. The method of claim 10 , wherein the cytotoxin is selected from the group consisting of paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin.
17. The method of claim 3 , wherein the antibody is conjugated to a cytotoxin.
18. The method of claim 17 , wherein the cytotoxin is selected from the group consisting of paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin.
19. The method of claim 3 , wherein the individual is human.
20. The method of claim 6 , wherein the antibody is conjugated to a cytotoxin.
21. The method of claim 20 , wherein the cytotoxin is selected from the group consisting of paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin.
22. The method of claim 6 , wherein the individual is human.
23. The method of claim 1 , wherein the cancer is colorectal cancer.
24. The method of claim 1 , wherein the cancer is gastric cancer.
25. The method of claim 3 , wherein the cancer is colorectal cancer.
26. The method of claim 3 , wherein the cancer is gastric cancer.
27. The method of claim 4 , wherein the cancer is colorectal cancer.
28. The method of claim 4 , wherein the cancer is gastric cancer.
29. The method of claim 6 , wherein the cancer is colorectal cancer.
30. The method of claim 6 , wherein the cancer is gastric cancer.