Combined use of anti-cytokine antibodies or antagonists and anti-CD20 for treatment of B cell lymphoma

Abstract

The present invention discloses combined therapies for treating hematologic malignancies, including B cell lymphomas and leukemias or solid non-hematologic tumors, comprising administration of anti-cytokine antibodies or antagonists to inhibit the activity of cytokines which play a role in perpetuating the activation of B cells. The administration of such antibodies and antagonists, particularly anti-IL10 antibodies and antagonists, is particularly useful for avoiding or decreasing the resistance of hematologic malignant cells or solid tumor cells to chemotherapeutic agents and anti-CD20 or anti-CD22 antibodies. The invention also provides combination therapies for solid tumors having B cell involvement comprising the administration of an anti-cytokine antibody and a B cell depleting antibody such as RITUXAN®.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims benefit of priority from U.S. Provisional Ser. No. 60 / 193,467, filed Mar. 31, 2000, and incorporated by reference herein.FIELD OF THE INVENTION [0002] The present invention concerns methods for treating hematologic malignancies including B cell lymphomas and leukemias with anti-cytokine agents such as antibodies and antagonists, where the targeted cytokines play a potentiating role in the disease process by stimulating hematologic malignant cells including B lymphoma and leukemia cells. Treatment with anti-cytokine agents in combination with other known therapies such as chemotherapy and administration of therapeutic antibodies has been found to provide a synergistic effect. [0003] The invention also embraces the treatment of solid non-hematologic (non-lymphoid) tumors, e.g., colorectal or liver cancer, which tumors are characterized by B cell involvement, by the administration of a cytokine antibody or cytokine a...

AI Technical Summary

Benefits of technology

[0017] It is an object of the invention to provide a method of avoiding, decreasing or overcoming the resistance of hematologic malignant cells or solid non-hematologic tumor cells to at least one chemotherapeutic agent, comprising administering an anti-cytokine antibody or cytokine antagonist to a patient diagnosed with a hematologic malignancy prior, concurrent or after administration of at least one chemotherapeutic agent.

[0018] It is a more specific object of the invention to provide a method of avoiding, decreasing or overcoming the resistance of hematologic malignant cells to apoptosis induced by a therapeutic agent, comprising administering an anti-cytokine antibody or cytokine antagonist to a patient diagnosed with a hematologic malignancy.

[0026] In a first aspect, the present invention relates to the administration of anti-cytokine antibodies and cytokine antagonists, particularly antibodies to IL10, in combination with chemotherapy drugs and / or therapeutic antibodies to increase the response rate and response duration in patients with hematological malignancies such as B cell lymphomas and leukemias or solid non-hematologic tumors, such as breast cancer, ovarian cancer, testicular cancer and others. Thus, the present invention relates to methods of treating hematologic malignancies such as B cell lymphomas and leukemias by administering to a patient having a hematologic malignancy such as B cell lymphoma or a leukemia, antibodies directed to B cell receptors and antibodies or antagonists which interfere with the action of certain cytokines. In particular, the present invention relates to administration of antibodies to B cell markers which initiate apoptosis of B lymphoma cells, such as anti-CD20, anti-CD22, anti-CD40, anti-CD23, anti-CD19, anti-CD37 and others identified infra, and antibodies to or antagonists of cytokines which may interfere with apoptosis, e.g., anti-IL10. Combined therapeutic regimens including other treatments which would also benefit from anti-cytokine therapy, i.e., chemotherapy, are also encompassed. The methods will find use in particular for treating patients having hematological malignancies such as B lymphomas or leukemias characterized by cells that have become resistant to chemotherapeutic agents and therapeutic antibodies.

Problems solved by technology

While patients often respond to conventional therapies, they usually relapse within several months.

However, many patients are refractory to or relapse following Rituximab® therapy, as well as chemotherapy.

However, some groups have also recognized that cytokines may play a detrimental role in the development of some cancers.

However, there have been just as many reports in the literature which have suggested that cytokines such as IL10 show no correlation to disease progression, and that such cytokines may actually be helpful in combating lymphoma rather than contributing to the disease.

Such combined treatment regimens would add to the therapies available to lymphoma patients and potentially decrease the rate of relapse in these patients.