Methods of therapy for cancers characterized by overexpression of the HER2 receptor protein

Abstract

Methods for treating a subject with a cancer that is characterized by overexpression of HER2 receptor protein using a combination of interleukin-2 (IL-2) or variant thereof and at least one anti-HER2 antibody or fragment thereof are provided. These anti-tumor agents are administered as two separate pharmaceutical compositions, one containing IL-2 (or variant thereof), the other containing at least one anti-HER2 antibody (or fragment thereof), according to a dosing regimen. Administering of these two agents together potentiates the effectiveness of the anti-HER2 antibody alone, resulting in a positive therapeutic response that is improved with respect to that observed with this anti-tumor agent.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation application of U.S. patent application Ser. No. 09 / 855,342, filed May 14, 2001 from which priority is claimed pursuant to 35 U.S.C. §120, which claims the benefit under 35 U.S.C. § 119(e)(1) of U.S. Provisional Application No. 60 / 204,284, filed May 15, 2000, which applications are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]The present invention is directed to methods of therapy for cell proliferative disorders, more particularly to concurrent therapy with interleukin-2 and monoclonal antibodies targeting the HER2 receptor protein to treat cancers characterized by overexpression of the HER2 receptor protein.BACKGROUND OF THE INVENTION[0003]Cancer research has shown an increasing interest in the use of monoclonal antibodies as a therapeutic. Raised in a similar fashion to diagnostic antibodies, therapeutic antibodies are aimed at specifically targeting tumor cells. The...

AI Technical Summary

Benefits of technology

The patent describes a method of treating cancer by giving a combination of interleukin-2 (IL-2) or a variant thereof and at least one anti-HER2 antibody or fragment thereof. This treatment results in a better therapeutic response than using the antibody alone. The two agents are given as separate pharmaceutical compositions, and the method involves administering them simultaneously. This combination therapy improves the effectiveness of the anti-HER2 antibody and leads to a positive therapeutic response.

Problems solved by technology

The use of therapeutic monoclonal antibodies has been hampered in the past primarily because of issues related to the antigenicity of the protein.

This so-called HAMA (human anti-mouse antibody) response has imposed a great limitation on the use of monoclonal antibodies, as repeated dosing is nearly always precluded.

In addition, serious complications, such as serum sickness, have been reported with the use of these agents.

However, high doses of IL-2 used to achieve positive therapeutic results with respect to tumor growth frequently cause severe toxicity effects, including capillary leak, hypotension, and neurological changes (see, for example, Duggan et al.

Although both of these agents exhibit promising anti-tumor activity, their therapeutic potential for cancer patients needs further examination.

Cancers whose cells overexpress the HER2 receptor can be particularly recalcitrant to treatment.

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