Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer

Citation
Jj. Bennett et al., Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer, J MOL MED-J, 78(3), 2000, pp. 166-174
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
JOURNAL OF MOLECULAR MEDICINE-JMM
ISSN journal
0946-2716 → ACNP
Volume
78
Issue
3
Year of publication
2000
Pages
166 - 174
Database
ISI
SICI code
0946-2716(2000)78:3<166:AEOROV>2.0.ZU;2-V
Abstract
Oncolytic viral therapy is a promising new method of cancer treatment. Peri toneal dissemination of cancer is a common and fatal clinical condition see n in many malignancies, with few effective therapies available. G207, a mul timutated replication-competent herpes simplex virus type-1, effectively tr eats disseminated peritoneal cancer This study evaluates viral proliferatio n and subsequent tumoricidal effects in vitro and in vivo after regional vi ral delivery. In vitro studies demonstrate that G207 efficiently kills five human gastric cancer cell lines, and that permissiveness to viral replicat ion is correlated with cytotoxicity. In a murine xenograft model of human g astric carcinomatosis, peritoneal delivery of G207 effectively kills tumor and prolongs survival. Data from quantitative PCR characterizes peritoneal clearance of virus after intraperitoneal injection, and identifies G207 rep lication within tumor cells in vivo, similar to in vitro proliferation. Fur ther analysis of various organs confirms that G207 does not replicate withi n normal tissue after peritoneal delivery. Wild-type KOS viral replication was also demonstrated in vivo, with significant toxicity secondary to disse mination and encephalitis. In vivo viral proliferation of G207 is restricte d to tumor cells, is correlated with in vitro assays, and is an important m echanism of anticancer efficacy.