Poliovirus receptor CD155-targeted oncolysis of glioma.
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.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Melinda K
MK
Merrill
Guenter
G
Bernhardt
John H
JH
Sampson
Carol J
CJ
Wikstrand
Darell D
DD
Bigner
Matthias
M
Gromeier
D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D008565:Membrane Proteins; D017955:Poliovirus / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012229:Rhinovirus / Q000235:genetics; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor