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Poliovirus receptor CD155-targeted oncolysis
of glioma
Melinda K. Merrill, Guenter Bernhardt, John H. Sampson, Carol J. Wikstrand,
Darell D. Bigner, Matthias Gromeier
Departments of Molecular
Genetics and Microbiology (M.K.M., M.G.), Surgery (J.H.S.), and Pathology
(C.J.W., D.D.B.), Duke University Medical Center, Durham, NC 27710, USA; and
Institute of Immunology, Hanover Medical University, 30625 Hanover, Germany
(G.B.)
Cell adhesion molecules of the immunoglobulin superfamily are aberrantly
expressed in malignant glioma.
Amongst these, the human poliovirus receptor CD155 provides a molecular target
for therapeutic intervention with oncolytic poliovirus recombinants.
Poliovirus has been genetically modified through insertion of regulatory
sequences derived from human rhinovirus type 2 to selectively replicate within
and destroy cancerous cells.
Efficacious oncolysis mediated by poliovirus derivatives depends on the presence
of CD155 in targeted tumors.
To prepare oncolytic polioviruses for clinical application, we have developed a
series of assays in high-grade malignant glioma (HGL) to characterize CD155
expression levels and susceptibility to oncolytic poliovirus recombinants.
Analysis of 6 HGL cases indicates that CD155 is expressed in these tumors and in
primary cell lines derived from these tumors.
Upregulation of the molecular target CD155 rendered explant cultures of all
studied tumors highly susceptible to a prototype oncolytic poliovirus
recombinant.
Our observations support the clinical application of such agents against HGL.
© 2004 Duke University Press
Source: http://caliban.ingentaselect.com/vl=3391422/cl=57/nw=1/rpsv/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n3/s4/p208
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