Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer Journal Article
| Authors: | Gholami, S.; Chen, C. H.; Lou, E.; De Brot, M.; Fujisawa, S.; Chen, N. G.; Szalay, A. A.; Fong, Y. |
| Article Title: | Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer |
| Abstract: | Objective: This study aimed to investigate the therapeutic impact of a new oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model and its potential for treating distant metastatic disease. Background: TNBCs are aggressive tumors associated with a high metastatic rate. Their lack of targets for hormonal/biological therapy presents significant clinical challenges and a dire need for novel therapies. Methods: GLV-1h153, a replication-competent vaccinia virus, was tested against multiple cell lines. Cytotoxicity and viral replication were determined. Intratumoral (IT) or intravenous (IV) injection of GLV-1h153 (1 × 10 plaque-forming units) or phosphate buffered saline was tested in an orthotopic murine model, which reliably produces systemic metastasis. Tumors, lymph nodes, and metastatic organs (lung, liver, and brain) were harvested 5 and 8 weeks after treatment and prepared for histopathological review. Demonstration of metastasis was performed using immunofluorescence and hematoxylin and eosin (H&E) staining. Results: GLV-1h153 infected, replicated in, and killed all TNBC cell lines in vitro. In vivo, mean tumor volume 2 weeks after treatment was 22 (IT), 29 (IV) versus 245 mm (control; P < 0.002). Five weeks after treatment, all harvested lymph nodes and organs showed no evidence of metastatic cells. All harvested tumors showed complete response to treatment, with only necrosis and fibrosis on H&E staining 8 weeks after treatment. Conclusions: This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV-1h153 is a promising therapeutic agent for preventing and treating metastatic TNBC and warrants further clinical testing in patients. © 2012 Lippincott Williams & Wilkins. |
| Keywords: | controlled study; protein expression; treatment response; unclassified drug; human cell; histopathology; nonhuman; treatment duration; conference paper; lymph node metastasis; animal cell; mouse; animal tissue; cell viability; tumor volume; animal experiment; animal model; cytotoxicity; immunofluorescence; in vitro study; liver metastasis; lung metastasis; brain metastasis; oncolytic virus; oncolytic virotherapy; vaccinia virus; virus replication; breast metastasis; triple negative breast cancer; glv 1h153; oncolytic viral therapy; glv-1h153; metastatic triple-negative breast cancer |
| Journal Title: | Annals of Surgery |
| Volume: | 256 |
| Issue: | 3 |
| ISSN: | 0003-4932 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2012-09-01 |
| Start Page: | 437 |
| End Page: | 445 |
| Language: | English |
| DOI: | 10.1097/SLA.0b013e3182654572 |
| PROVIDER: | scopus |
| PUBMED: | 22868370 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2012" - "CODEN: ANSUA" - "Source: Scopus" |
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