Methods for treating cancer using anti-Wnt2 monoclonal antibodies and siRNA

Abstract

This invention relates to methods of inhibiting the growth of cells, in particular cancer cells, that overexpress Wnt2. The methods comprise contacting the cell with an agent that binds to Wnt2 mRNA or Wnt2 protein, interferes with Wnt2 signaling or inhibits binding of the Wnt2 protein to another protein, such as a Frizzled receptor.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims benefit of provisional application Ser. No. 60 / 571,323, filed May 14, 2004, the disclosure of which is incorporated in its entirety herein by reference.FIELD OF THE INVENTION [0002] This invention relates to methods of inhibiting the growth of cancer cells that overexpress Wnt2 protein. The methods comprise contacting the cell with an agent that binds to Wnt2 mRNA or Wnt2 protein, interferes with Wnt2 signaling, or inhibits binding of the Wnt2 protein to other proteins, such as the Frizzled receptor. BACKGROUND OF THE INVENTION [0003] Lung Cancer is the leading cause of cancer death in the United States and worldwide, with >170,000 newly diagnosed cases each year in the US and nearly a million cases worldwide (Minna et al. Cancer Cell. 1(1):49-52 (2002)). Despite aggressive approaches made in the therapy of lung cancer in the past decades, the 5-year survival rate for lung cancer remains under 15% (Minna et al...

AI Technical Summary

Benefits of technology

[0014] This invention provides a method of inhibiting the proliferation of a cell that overexpresses a Wnt2. The method compri

Problems solved by technology

Surgery, chemotherapy, and radiation have been used with generally unsatisfactory results in advanced disease.

Since MPM usually presents at an advanced stage, a curative resection is rarely possible.

Radiotherapy has failed to show clinical benefit as a single treatment modality, and the administration of chemotherapy is mostly restricted to the advanced stage with limited efficiency (Kindler, Lung Cancer 45 Suppl 1:S125-7 (2004)).

Alternative strategies based on pleural injections of recombinant cytokines have similarly proven unsatisfactory (Bard et al.

Since current interventions offer only limited benefit, and overall survival is low, there is an urgent need to develop new therapeutic agents based on a greater understanding of MPM's underlying molecular mechanisms.

However, the use of polyclonal and monoclonal antibodies in humans is severely restricted when the polyclonal monoclonal antibodies are produced in a non-human animal.

Repeated injections in humans of a “foreign” antibody, such as a mouse antibody, may lead to harmful hypersensitivity reactions, i.e., human anti-mouse antibody (HAMA) or an anti-idiotypic, response.

The HAMA response makes repeated administrations ineffective due to an increased rate of clearance from the patient's serum and / or allergic reactions by the patient.

Unfortunately, yields of monoclonal antibodies from human hybridoma cell lines are relatively low compared to mouse hybridomas.

Additionally, human cell lines expressing immunoglobulins are relatively unstable compared to mouse cell lines, and the antibody producing capability of these human cell lines is transient.

Thus, while human immunoglobulins are highly desirable, human hybridoma techniques have not yet reached the stage where human monoclonal antibodies with the required antigenic specificities can be easily obtained.

Thus, the prior art fails to provide clear evidence that compounds that modulate the Wnt2 pathway could be useful for example, for the treatment of cancer.

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