Intergeneric poliovirus recombinants for the treatment of malignant glioma
- Matthias Gromeier*,†,
- Sylvie Lachmann*,‡,
- Myrna R. Rosenfeld§,¶,
- Philip H. Gutin‖, and
- Eckard Wimmer*,**
- *Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, NY 11794; §Department of Neurosciences, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021; and ‖Neurosurgery Service, Department of Surgery, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10021
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Edited by Peter K. Vogt, The Scripps Research Institute, La Jolla, CA, and approved March 29, 2000 (received for review August 2, 1999)
Abstract
Poliovirus neuropathogenicity depends on sequences within the 5′ nontranslated region of the virus. Exchange of the poliovirus internal ribosomal entry site with its counterpart from human rhinovirus type 2 resulted in attenuation of neurovirulence in primates. Despite deficient virus propagation in cells of neuronal origin, nonpathogenic polio recombinants retain excellent growth characteristics in cell lines derived from glial neoplasms. Susceptibility of malignant glioma cells to poliovirus may be mediated by expression of a poliovirus receptor, CD155, in glial neoplasms. Intergeneric polio recombinants with heterologous internal ribosomal entry site elements unfolded strong oncolytic potential against experimentally induced gliomas in athymic mice. Our observations suggest that highly attenuated poliovirus recombinants may have applicability as biotherapeutic antineoplastic agents.
Footnotes
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↵ † Present address: Department of Microbiology, Duke University Medical Center, Durham, NC 27710.
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↵ ‡ Present address: Deutsches Krebsforschungszentrum, 69009 Heidelberg, Germany.
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↵ ¶ Present address: Department of Neurology, School of Medicine, University of Arkansas, Little Rock, AK 72205.
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↵ ** To whom reprint requests should be addressed. E-mail: ewimmer{at}ms.cc.sunysb.edu.
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This paper was submitted directly (Track II) to the PNAS office.
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See commentary on page 6242.
- Abbreviations:
- IRES,
- internal ribosomal entry site;
- pfu,
- plaque-forming unit
- Copyright © 2000, The National Academy of Sciences
