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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-2-20
pubmed:abstractText
The receptor protein tyrosine phosphatase beta (RPTPbeta) is a functional biomarker for several solid tumor types. RPTPbeta expression is largely restricted to the central nervous system and overexpressed primarily in astrocytic tumors. RPTPbeta is known to facilitate tumor cell adhesion and migration through interactions with extracellular matrix components and the growth factor pleiotrophin. Here, we show that RPTPbeta is expressed in a variety of solid tumor types with low expression in normal tissue. To assess RPTPbeta as a potential target for treatment of glioblastoma and other cancers, antibodies directed to RPTPbeta have been developed and profiled in vitro and in vivo. The recombinant extracellular domain of human short RPTPbeta was used to immunize mice and generate monoclonal antibodies that selectively recognize RPTPbeta 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-RPTPbeta 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2271-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16489031-Animals, pubmed-meshheading:16489031-Antibodies, Monoclonal, pubmed-meshheading:16489031-Antibody Specificity, pubmed-meshheading:16489031-Cell Line, Tumor, pubmed-meshheading:16489031-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:16489031-Female, pubmed-meshheading:16489031-Flow Cytometry, pubmed-meshheading:16489031-Glioblastoma, pubmed-meshheading:16489031-Humans, pubmed-meshheading:16489031-Immunization, pubmed-meshheading:16489031-Immunotoxins, pubmed-meshheading:16489031-Mice, pubmed-meshheading:16489031-Mice, Inbred BALB C, pubmed-meshheading:16489031-Mice, Nude, pubmed-meshheading:16489031-Nerve Tissue Proteins, pubmed-meshheading:16489031-Protein Tyrosine Phosphatases, pubmed-meshheading:16489031-Receptor-Like Protein Tyrosine Phosphatases, Class 5, pubmed-meshheading:16489031-Xenograft Model Antitumor Assays
pubmed:year
2006
pubmed:articleTitle
Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a glioblastoma model.
pubmed:affiliation
AGY Therapeutics, Inc., South San Francisco, California 94080, USA. efoehr@agyinc.com
pubmed:publicationType
Journal Article