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Abstract

In the past 5 years, the field of oncolytic virus research has matured significantly and is moving past the stage of being a laboratory novelty into a new era of preclinical and clinical trials. What have recent anticancer trials of oncolytic viruses taught us about this exciting new line of therapeutics?

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Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5.

J M Bergelson, J. A. Cunningham, G Droguett … (1997)

A complementary DNA clone has been isolated that encodes a coxsackievirus and adenovirus receptor (CAR). When transfected with CAR complementary DNA, nonpermissive hamster cells became susceptible to coxsackie B virus attachment and infection. Furthermore, consistent with previous studies demonstrating that adenovirus infection depends on attachment of a viral fiber to the target cell, CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and showed a 100-fold increase in susceptibility to virus-mediated gene transfer. Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.

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VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents.

David Stojdl, Brian Lichty, Benjamin tenOever … (2003)

Ideally, an oncolytic virus will replicate preferentially in malignant cells, have the ability to treat disseminated metastases, and ultimately be cleared by the patient. Here we present evidence that the attenuated vesicular stomatitis strains, AV1 and AV2, embody all of these traits. We uncover the mechanism by which these mutants are selectively attenuated in interferon-responsive cells while remaining highly lytic in 80% of human tumor cell lines tested. AV1 and AV2 were tested in a xenograft model of human ovarian cancer and in an immune competent mouse model of metastatic colon cancer. While highly attenuated for growth in normal mice, both AV1 and AV2 effected complete and durable cures in the majority of treated animals when delivered systemically.

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Experimental therapy of human glioma by means of a genetically engineered virus mutant.

R Martuza, A. Malick, J M Markert … (1991)

Malignant gliomas are the most common malignant brain tumors and are almost always fatal. A thymidine kinase-negative mutant of herpes simplex virus-1 (dlsptk) that is attenuated for neurovirulence was tested as a possible treatment for gliomas. In cell culture, dlsptk killed two long-term human glioma lines and three short-term human glioma cell populations. In nude mice with implanted subcutaneous and subrenal U87 human gliomas, intraneoplastic inoculation of dlsptk caused growth inhibition. In nude mice with intracranial U87 gliomas, intraneoplastic inoculation of dlsptk prolonged survival. Genetically engineered viruses such as dlsptk merit further evaluation as novel antineoplastic agents.

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PubMed ID:: 16294217

DOI:: 10.1038/nrc1750

ScienceOpen disciplines: Chemistry

Keywords: Animals,Clinical Trials as Topic,Genetic Variation,Humans,Linkage Disequilibrium,Neoplasms,therapy,virology,Oncolytic Virotherapy,Oncolytic Viruses,physiology,Risk Factors

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ScienceOpen disciplines: Chemistry

Keywords: Animals, Clinical Trials as Topic, Genetic Variation, Humans, Linkage Disequilibrium, Neoplasms, therapy, virology, Oncolytic Virotherapy, Oncolytic Viruses, physiology, Risk Factors

Recent progress in the battle between oncolytic viruses and tumours.

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Most cited references 100

Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5.

VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents.

Experimental therapy of human glioma by means of a genetically engineered virus mutant.

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