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Neuro-Oncology 2004 6(3):208-217; doi:10.1215/S1152851703000577
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© 2004 by the Society forNeuro-Oncology

Poliovirus receptor CD155-targeted oncolysis of glioma

Melinda K. Merrill, Guenter Bernhardt, John H. Sampson, Carol J. Wikstrand, Darell D. Bigner and Matthias Gromeier2

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.)

2 Address correspondence to Matthias Gromeier, Department of Molecular Geneticsand Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710(grome001{at}mc.duke.edu).


  Abstract

Cell adhesion molecules of the immunoglobulin superfamily are aberrantlyexpressed in malignant glioma. Amongst these, the human poliovirus receptorCD155 provides a molecular target for therapeutic intervention with oncolyticpoliovirus recombinants. Poliovirus has been genetically modified throughinsertion of regulatory sequences derived from human rhinovirus type 2 toselectively replicate within and destroy cancerous cells. Efficaciousoncolysis mediated by poliovirus derivatives depends on the presence of CD155in targeted tumors. To prepare oncolytic polioviruses for clinicalapplication, we have developed a series of assays in high-grade malignantglioma (HGL) to characterize CD155 expression levels and susceptibility tooncolytic poliovirus recombinants. Analysis of 6 HGL cases indicates thatCD155 is expressed in these tumors and in primary cell lines derived fromthese tumors. Upregulation of the molecular target CD155 rendered explantcultures of all studied tumors highly susceptible to a prototype oncolyticpoliovirus recombinant. Our observations support the clinical application ofsuch agents against HGL.

Received October 15, 2003; Accepted January 7, 2004


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