Method of treating lewis Y-expressing tumors
View Patent ↗The invention relates to a monoclonal antibody or derivative or fragment thereof that is derived from a parental monoclonal antibody, that recognizes the Lewis Y antigen, characterized in that the Fc region or region equivalent to the Fc region of said antibody or derivative or fragment thereof carries a bi-sected hybrid type N-glycosylation pattern and that said antibody shows at least 10 fold increased ADCC and at least 10% reduced CDC activity.
1. A method of treating a Lewis Y-expressing tumor in a patient in need of such treatment, which comprises administering to said patient a monoclonal antibody or fragment thereof that recognizes the Lewis Y antigen and is derived from a parental monoclonal antibody that recognizes the Lewis Y antigen, characterized in that the Fc region of said antibody or fragment thereof carries a bi-sected hybrid type N-glycosylation pattern and that said antibody shows at least 10 fold increased ADCC and at least 10% reduced CDC activity as compared to the ADCC and CDC activity of said parental monoclonal antibody, wherein said antibody or fragment thereof stimulates the reduction or inhibition of the growth of tumor cells in said patient.
2. The method according to claim 1 , wherein said tumor is a solid cancer.
3. The method according to claim 2 , wherein said solid cancer is of epithelial origin.
4. The method according to claim 1 for treating a minimal residual disease.
5. The method according to claim 1 for passive immunotherapy.
6. The method according to claim 1 , wherein said antibody is administered in a dosage of at least 50 mg/dose.
7. The method according to claim 1 , wherein said antibody is administered in a dosage of at least 100 mg/dose.
8. The method according to claim 1 , wherein said antibody is administered in a dosage of at least 200 mg/dose.
9. The method according to claim 1 , characterized in that the ADCC activity of the antibody is increased at least 20 fold.
10. The method according to claim 1 , characterized In that the ADCC activity of the antibody is increased at least 25 fold.
11. The method according to claim 1 , characterized in that the ADCC activity of the antibody is increased at least 40 fold.
12. The method according to claim 1 , characterized in that the ADCC activity of the antibody is increased at least 60 fold.
13. The method according to claim 1 , characterized in that the CDC activity of the antibody is at least 20% decreased.
14. The method according to claim 1 , characterized in that the CDC activity of the antibody is at least 40% decreased.
15. The method according to claim 1 , characterized in that the antibody or fragment carries a bi-secting N-acetylglucosamine group.
16. The method according to claim 1 , characterized in that the antibody is a humanized antibody.
17. The method according to claim 1 wherein the antibody is IgG or a fragment thereof.
18. The method according to claim 17 wherein the antibody is IgG1 or a fragment thereof.
19. The method of claim 1 wherein said antibody does not contain a core fucosylation.
20. The method of using a monoclonal antibody or fragment thereof that recognizes the Lewis Y antigen and is derived from a parental monoclonal antibody that recognizes the Lewis Y antigen, characterized in that the Fc region of said antibody or fragment thereof carries a bi-sected hybrid type N-glycosylation pattern and that said antibody shows at least 10 fold increased ADCC and at least 10% reduced CDC activity as compared to the ADCC and CDC activity of said parental monoclonal antibody as a pharmaceutical to treat a Lewis Y-expressing tumor.