Targeting of the receptor protein tyrosine phosphatase β with a monoclonal antibody delays tumor growth in a glioblastoma model

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