Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy

Citation
Ka. Delman et al., Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy, HUM GENE TH, 11(18), 2000, pp. 2465-2472
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENE THERAPY
ISSN journal
1043-0342 → ACNP
Volume
11
Issue
18
Year of publication
2000
Pages
2465 - 2472
Database
ISI
SICI code
1043-0342(200012)11:18<2465:EOPIOT>2.0.ZU;2-I
Abstract
Herpes simplex viruses (HSV) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. They are natural human pathogens and the majority of adults have anti-HSV immunity. The cur rent study examined the effect of preexisting immunity on the response to h erpes-based oncolytic viral treatment of hepatic metastatic cancer in a mur ine model designed to simulate a clinical approach likely to be utilized fo r nonneurological tumors. Specifically, the anticancer effects of NV1020 or G207, two multimutated HSV-1 oncolytic viruses, were tested in immunocompe tent mice previously immunized with a wild-type herpes simplex type 1 virus . Mice were documented to have humoral as well as cell-mediated immunity to HSV-1. Tumor response to oncolytic therapy was not measurably abrogated by immunity to HSV at the doses tested. The influence of route of viral admin istration was also tested in models of regional hepatic arterial and intrav enous therapy. Route of viral administration influenced efficacy, as virus delivered intravenously produced some detectable attenuation while hepatic arterial therapy remained unaffected. These results demonstrate that when g iven at appropriate doses and in reasonable proximity to tumor targets, HSV -based oncolytic therapy can still be expected to be effective treatment fo r patients with hepatic malignancies.