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Vaccinia Virus GLV-1h153 Is Effective in Treating and Preventing Metastatic Triple-Negative Breast Cancer

Gholami, Sepideh MD*; Chen, Chun-Hao MD*; Lou, Emil MD, PhD; De Brot, Marina MD*; Fujisawa, Sho PhD; Chen, Nanhai G. PhD§; Szalay, Aladar A. PhD§,‖; Fong, Yuman MD*

doi: 10.1097/SLA.0b013e3182654572
Papers of the 132nd ASA Annual Meeting

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 × 107 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 mm3 (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.

This study demonstrates that a single intratumoral or intravenous injection of a novel oncolytic vaccinia virus, GLV-1h153, not only causes significant regression of primary triple-negative breast tumors but also prevents and treats metastatic disease in an orthotopic murine cancer model.

*Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY

Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN

Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY

§Department of Radiation Oncology, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego

Rudolf Virchow Center for Experimental Biomedicine, Department of Biochemistry and Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.

Reprints: Yuman Fong, MD, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065. E-mail: Fongy@mskcc.org.

Disclosure: This study was partly supported by a grant from the Goodwin Foundation and a grant from the Flight Attendant Medical Research Institute.

© 2012 Lippincott Williams & Wilkins, Inc.