Treatment of B-cell associated diseases
View Patent ↗Treatment of B-cell associated diseases including autoimmune and B-cell malignancies such as leukemias, lymphomas, using the combination of an anti-CD20 antibody, preferably RITUXAN® and a radiolabeled anti-CD22 antibody, preferably an 90 Y labeled humanized anti-CD22 antibody, is described. These therapeutic regimens provide for enhanced depletion of B cells, and therefore reduce the risk in B cell malignancy treatment of relapse associated with RITUXAN® and, moreover, provide for prolonged immunosuppression of B-cell immune responses, especially in the context of autoimmune diseases and transplant.
1. A method of treating a subject having an autoimmune disease comprising the steps of:
(i) administering a therapeutically effective amount of cold (non-radiolabeled) anti-CD20 monoclonal antibody having at least 20% of the B cell depleting activity of a C2B8 antibody; and
(ii) administering a therapeutically effective amount of a hot (radiolabeled) anti-CD22 antibody or fragment thereof;
wherein said anti-CD20 antibody and said radiolabeled anti-CD22 antibody or fragment are administered separately or in combination, and in either order.
2. The method of claim 1 , wherein the amount of said cold anti-CD20 antibody ranges from 0.1 mg to 500 mg/m 2 per week.
3. The method of claim 2 , wherein the amount of said cold anti-CD20 antibody is at least about 500 mg/m 2 weekly.
4. The method of claim 3 , wherein said amount is about 375 mg/m 2 weekly for four weeks.
5. The method of claim 1 , wherein said radio labeled anti-CD22 antibody or fragment is an yttrium-labeled anti-CD22 antibody or fragment.
6. The method of claim 2 , wherein said radiolabeled anti-CD22 antibody fragment is a Fab 2 , Fab, Fv, or domain deleted antibody.
7. The method of claim 5 , wherein said anti-CD22 antibody is a 90 Y labeled humanized LL2 antibody.
8. The method of claim 7 , wherein the dosage of said radiolabeled antibody ranges from 10 to 30 mCi.
9. The method of claim 8 , wherein said radiolabeled anti-CD22 antibody is administered about a week after a C2B8 antibody therapeutic regimen has been completed.
10. The method of claim 1 wherein the anti-CD20 antibody is C2B8.
11. The method of claim 1 wherein the autoimmune disease is a B cell related autoimmune disease.
12. The method of claim 1 , wherein the cold (non-radiolabeled) anti-CD20 monoclonal antibody has at least 90% of the B cell depleting activity of a C2B8 antibody.