Novel oncolytic agent GLV-1h68 is effective against malignant pleural mesothelioma Journal Article
| Authors: | Kelly, K. J.; Woo, Y.; Brader, P.; Yu, Z.; Riedl, C.; Lin, S. F.; Chen, N.; Yu, Y. A.; Rusch, V. W.; Szalay, A. A.; Fong, Y. |
| Article Title: | Novel oncolytic agent GLV-1h68 is effective against malignant pleural mesothelioma |
| Abstract: | Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carrying transgenes encoding Renilla luciferase, green fluorescent protein (both inserted at the F14.5L locus), β-galactosidase (inserted at the J2R locus, which encodes thymidine kinase), and β-glucuronidase (at the A56R locus, which encodes hemagglutinin). This virus was tested in six human MPM cell lines (MSTO-211H, VAMT, JMN, H-2373, H-2452, and H-2052). GLV-1h68 successfully infected all cell lines. For the most sensitive line, MSTO-211H, expression of green fluorescent protein (GFP) started within 4 hr with increasing intensity over time until nearly 100% of cells expressed GFP at 24 hr. All cell lines were sensitive to killing by GLV-1h68, with the degree of sensitivity predictable by infectivity assay. Even the most resistant cell line exhibited 44 ± 3.8% cell survival by day 7 when infected at a multiplicity of infection of 1.0. Viral proliferation assays demonstrated 2-to 4-fold logarithmic replication of GLV-1h68 in the cell lines tested. In an orthotopic model, GLV-1h68 effectively prevented development of cachexia and tumor-related morbidity, reduced tumor burden, and cured MPM in both early and late treatment groups. GLV-1h68 was successfully used to treat MPM in vitro and in an orthotopic model (in vivo). These promising results warrant clinical investigation of GLV-1h68 as a novel agent in the treatment of MPM. © Mary Ann Liebert, Inc. 2008. |
| Keywords: | cancer survival; controlled study; treatment outcome; unclassified drug; human cell; nonhuman; antineoplastic agent; animal cell; mouse; animals; mice; animal tissue; tumor volume; morbidity; green fluorescent protein; animal experiment; animal model; gene locus; in vivo study; cytotoxicity; in vitro study; cell line, tumor; human cell culture; cancer vaccine; genetic engineering; mice, nude; transgene; beta galactosidase; oncolytic virotherapy; pleura mesothelioma; vaccinia virus; mesothelioma; green fluorescent proteins; cachexia; virus recombinant; virus replication; gene insertion; body burden; pleural neoplasms; transgenes; virus protein; renilla luciferin 2 monooxygenase; renilla luciferase; giardia lamblia virus; beta-galactosidase; virus gene; beta glucuronidase; glucuronidase; luciferases, renilla; virus protein glv 1h68; orthotopic transplantation |
| Journal Title: | Human Gene Therapy |
| Volume: | 19 |
| Issue: | 8 |
| ISSN: | 1043-0342 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2008-08-01 |
| Start Page: | 774 |
| End Page: | 782 |
| Language: | English |
| DOI: | 10.1089/hum.2008.036 |
| PUBMED: | 18754710 |
| PROVIDER: | scopus |
| PMCID: | PMC2940611 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "CODEN: HGTHE" - "Source: Scopus" |
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