Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model Journal Article
| Authors: | Ebright, M. I.; Zager, J. S.; Malhotra, S.; Delman, K. A.; Weigel, T. L.; Rusch, V. W.; Fong, Y. |
| Article Title: | Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model |
| Abstract: | Objective: Innovative treatments are needed for metastatic disease involving the pleura. NV1020 is a novel, multimutated, replication-restricted herpes simplex virus under investigation for its ability to selectively kill tumors by means of direct cell lysis. This study examines NV1020 in a rat model of pleura-based lung cancer. Methods: Cytotoxicity and viral proliferation were evaluated in vitro by exposure of the human non-small cell lung cancer cell line A549 to virus. NV1020 was also tested in an in vivo pleura-based cancer model established by injecting 1 x 107 A549 cells into the thoracic cavity of nude rats. Intrapleural treatments (1 X 107 viral particles) were given 3 hours or 3 days after tumor injection to model treatment of microscopic or macroscopic disease (n = 8-9/group). Tumor burden was assessed at 5 weeks. NV1020 infection and dissemination within the thoracic cavity was determined by means of immunohistochemistry. Results: In vitro, at multiplicities of infection (viral particles per tumor cell) of 0.01, 0.1, and 1.0, cell killing of A549 by NV1020 was 66%, 90%, and 97%, respectively, at 7 days after infection. Viral burst occurred by day 2. Intrapleural treatment was effective for both the microscopic (P < .001) and macroscopic (P < .05) in vivo tumor models. Virus was detectable by means of immunohistochemistry in tumors but not in adjacent normal intrathoracic tissues. Conclusions: NV1020 is not only highly cytotoxic to the human lung cancer line A549 in vitro but can be delivered in a clinically relevant fashion to safely and effectively treat pleura-based tumor in vivo in a rat model. |
| Keywords: | immunohistochemistry; controlled study; nonhuman; adenocarcinoma; animals; cell line; animal model; cytotoxicity; cancer model; cancer therapy; histology; cancer cell; rat; oncolytic virus; herpes virus; simplexvirus; rats; rats, nude; virus replication; neoplasm transplantation; herpes simplex virus 1; virus particle; pleural neoplasms; pleura cancer; virus dna; virion; humans; male; priority journal; article; herpes virus nv1020 |
| Journal Title: | Journal of Thoracic and Cardiovascular Surgery |
| Volume: | 124 |
| Issue: | 1 |
| ISSN: | 0022-5223 |
| Publisher: | Mosby Elsevier |
| Date Published: | 2002-07-01 |
| Start Page: | 123 |
| End Page: | 129 |
| Language: | English |
| DOI: | 10.1067/mtc.2002.122297 |
| PUBMED: | 12091817 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Presented at the 81st Annual Meeting of The American Association for Thoracic Surgery; 2001 May 6-9; San Diego, CA -- Export Date: 14 November 2014 -- Source: Scopus |
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