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Targeting of the Receptor Protein Tyrosine Phosphatase ß with a Monoclonal Antibody Delays Tumor Growth in a Glioblastoma Model

AGY Therapeutics, Inc., South San Francisco, California

Requests for reprints: Erik D. Foehr, AGY Therapeutics, Drug Discovery, 270 East Grand Avenue, South San Francisco, CA 94080. Phone: 650-228-1173; Fax: 650-615-4544; E-mail: efoehr{at}agyinc.com.

The receptor protein tyrosine phosphatase ß (RPTPß) is a functional biomarker for several solid tumor types. RPTPß expression is largely restricted to the central nervous system and overexpressed primarily in astrocytic tumors. RPTPß is known to facilitate tumor cell adhesion and migration through interactions with extracellular matrix components and the growth factor pleiotrophin. Here, we show that RPTPß is expressed in a variety of solid tumor types with low expression in normal tissue. To assess RPTPß as a potential target for treatment of glioblastoma and other cancers, antibodies directed to RPTPß have been developed and profiled in vitro and in vivo. The recombinant extracellular domain of human short RPTPß was used to immunize mice and generate monoclonal antibodies that selectively recognize RPTPß and bind to the antigen with low nanomolar affinities. Moreover, these antibodies recognized the target on living tumor cells as measured by flow cytometry. These antibodies killed glioma cells in vitro when coupled to the cytotoxin saporin either directly or via a secondary antibody. Finally, in vivo studies showed that an anti-RPTPß immunotoxin (7E4B11-SAP) could significantly delay human U87 glioma tumors in a mouse xenograft model. Unconjugated 7E4B11 provides a modest but statistically significant tumor growth delay when delivered systemically in mice bearing U87 glioma tumors. (Cancer Res 2006; 66(4): 2271-8)

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