Regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus GLV-1h68 Journal Article
| Authors: | Yu, Y. A.; Galanis, C.; Woo, Y.; Chen, N.; Zhang, Q.; Fong, Y.; Szalay, A. A. |
| Article Title: | Regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus GLV-1h68 |
| Abstract: | Oncolytic virotherapy of tumors has shown promising results in both preclinical and clinical studies. Here, we investigated the therapeutic efficacy of a replication-competent vaccinia virus, GLV-1h68, against human pancreatic carcinomas in cell cultures and in nude mice. We found that GLV-1h68 was able to infect, replicate in, andlyse tumor cells in vitro. Virus-mediated marker gene expressions were readily detected. Moreover, s.c. PANC-1 pancreatic tumor xenografts were effectively treated by a single i.v. dose of GLV-1h68. Cancer killing was achieved with minimal toxicity. Viral titer analyses in homogenized organs and PANC-1 tumors showed that the mutant virus resides almost exclusively in the tumors and not in healthy organs. Except mild spleen enlargements, no histopathology changes were observed in any other organs 2 months after virus injection. Surprisingly, s.c. MIA PaCa-2 pancreatic tumors were treated with similar efficiency as PANC-1 tumors, although they differ significantly in sensitivity to viral lysis in cell cultures. When GLV-1h68 oncolytic viral therapy was used together with cisplatin or gemcitabine to treat PANC-1 tumors, the combination therapy resulted in enhanced and accelerated therapeutic results compared with the virus treatment alone. Profiling of proteins related to immune response revealed a significant proinflammatory immune response and marked activation of innate immunity in virus-colonized tumors. In conclusion, the GLV-1h68 strain showed outstanding therapeutic effects and a documented safety profile in mice, with great promise for future clinical development. Copyright © 2009 American Association for Cancer Research. |
| Keywords: | controlled study; unclassified drug; human cell; histopathology; cisplatin; nonhuman; gemcitabine; pancreatic neoplasms; biological marker; mouse; animals; mice; animal tissue; gene expression; tumor volume; animal experiment; inflammation; in vitro study; drug effect; xenograft model antitumor assays; cell line, tumor; pancreas carcinoma; cancer regression; immune response; human cell culture; mice, nude; splenomegaly; beta galactosidase; oncolytic virus; oncolytic virotherapy; vaccinia virus; cytolysis; innate immunity; virus infection; glv 1h68; virus replication; deoxycytidine; genetic markers; injections, intravenous; viral proteins; gene expression regulation, viral; vaccinia |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 8 |
| Issue: | 1 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-01-01 |
| Start Page: | 141 |
| End Page: | 151 |
| Language: | English |
| DOI: | 10.1158/1535-7163.mct-08-0533 |
| PUBMED: | 19139123 |
| PROVIDER: | scopus |
| PMCID: | PMC2664310 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 30 November 2010" - "CODEN: MCTOC" - "Source: Scopus" |
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