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

The receptor protein tyrosine phosphatase B (RPTPB) is a functional biomarker for several solid tumor types. RPTPB expression is largely restricted to the central nervous system and overexpressed primarily in astrocytic tumors. RPTPB is known to facilitate tumor cell adhesion and migration through interactions with extracellular matrix components and the growth factor pleiotrophin. Here, we show that RPTPB is expressed in a variety of solid tumor types with low expression in normal tissue. To assess RPTPB as a potential target for treatment of glioblastoma and other cancers, antibodies directed to RPTPB have been developed and profiled in vitro and in vivo. The recombinant extracellular domain of human short RPTPB was used to immunize mice and generate monoclonal antibodies that selectively recognize RPTPB 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-RPTPB 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)