Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer

Sepideh Gholami, Chun Hao Chen, Emil Lou, Marina De Brot, Sho Fujisawa, Nanhai G. Chen, Aladar A. Szalay, Yuman Fong

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalAnnals of Surgery
Volume256
Issue number3
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • GLV-1h153
  • metastatic triple-negative breast cancer
  • oncolytic viral therapy
  • vaccinia virus

ASJC Scopus subject areas

  • Surgery

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    Gholami, S., Chen, C. H., Lou, E., De Brot, M., Fujisawa, S., Chen, N. G., Szalay, A. A., & Fong, Y. (2012). Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer. Annals of Surgery, 256(3), 437-445. https://doi.org/10.1097/SLA.0b013e3182654572