Immunotherapy of b cell malignancies and autoimmune diseases using unconjugated antibodies and conjugated antibodies and antibody combinations and fusion proteins

Abstract

The invention is directed to a method for treating a treating and diagnosing a B cell-related disease, T cell-related disease or an autoimmune disease in a mammal by concurrently or sequentially administering to the mammal a therapeutic composition that comprises a pharmaceutically acceptable vehicle and at least one conjugated antibody, wherein predosing with a non-radiolabeled antibody is not performed.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is based on U.S. patent application Ser. No. 10 / 747,199, filed Dec. 30, 2003, which is based on U.S. provisional patent application Ser. No. 60 / 437,145, filed Dec. 31, 2002. The entire contents of these applications, including their specification, claims and drawings, are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to immunotherapeutic method for treating B-cell related malignancies, particularly aggressive non-Hodgkin's lymphomas. In particular, this invention is directed to methods for treating and diagnosing a B cell-related disease, T cell-related disease or an autoimmune disease in a mammal by administering to the mammal a therapeutic composition, wherein predosing with a non-radiolabeled antibody is not performed.BACKGROUND OF THE INVENTION[0003]B-cell lymphomas express surface antigens that have shown to be good targets for therapy with monoclonal ant...

AI Technical Summary

Benefits of technology

The present invention provides methods for treating diseases in mammals by administering a therapeutic composition that comprises a pharmaceutically acceptable vehicle and at least one conjugated antibody or fusion protein. The methods do not require predosing with a non-radiolabeled antibody and can be used against various antigens and disease states. The therapeutic compositions can be administered as a single agent or in combination with other therapeutic agents. The methods can be used in humans and domestic or companion animals. The invention also provides a method for treating aggressive non-Hodgkin's lymphoma, a method that works better than previous treatments.

Problems solved by technology

A Mab with longer half-life gives a longer residence time of the radioimmunoconjugate in blood and bone marrow and probably thus induces more toxicity.

Both products have shown a higher and more durable responses than naked antibodies, however, they also have dose-limiting toxicity, predominantly myelotoxicity.

Although these clinical studies suggest that fractionated therapy of a radioimmunoconjugate is feasible, no comparison was made with administered a single high-dose of the radioimmunoconjugate in terms of safety and efficacy.

Therefore, it was not interpretable from these studies whether or not any predosing was needed for such radioimmunotherapy, particularly with CD22 antibodies.