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ACS: Vaccinia Virus Studied for Triple-Negative Breast Cancer

Last Updated: October 03, 2012.

 

Combined oncolytic and antiangiogenic activity of new vacinnia virus targeting VEGF shows promise in mice

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A novel oncolytic vaccinia virus, GLV-1h164, encoding a single-chain antibody against vascular endothelial growth factor, is active in a murine model of triple-negative breast cancer, according to a study presented at the annual meeting of the American College of Surgeons, held from Sept. 30 to Oct. 4 in Chicago.

WEDNESDAY, Oct. 3 (HealthDay News) -- A novel oncolytic vaccinia virus (VACV), GLV-1h164, encoding a single-chain antibody against vascular endothelial growth factor, is active in a murine model of triple-negative breast cancer (TNBC), according to a study presented at the annual meeting of the American College of Surgeons, held from Sept. 30 to Oct. 4 in Chicago.

Sepideh Gholami, M.D., from the Memorial Sloan-Kettering Cancer Center in New York City, and colleagues examined the therapeutic effect of GLV-1h164 in a TNBC murine model. Viral infectivity, cytotoxicity, and replication were assessed when the VACV was tested against multiple TNBC cell lines. Mammary fat pad tumors were generated in athymic nude mice, and tumor growth was followed after treatment with GLV-1h164, its parent virus GLV-1h100, or phosphate-buffered saline (PBS).

The researchers found that viral infectivity was time- and concentration-dependent. TNBC cells lines were killed by GLV-1h164 in a dose-dependent manner, with more than 90 percent cytotoxicity within four days at a multiplicity of infection of five plaque-forming units/cell. The cytotoxicity of GLV-1h164 was identical to GLV-1h100 in vitro. In all cell lines, GLV-1h164 replicated efficiently, with more than a 400-fold increase observed within four days in viral copy numbers from the initial viral dose. In vivo, the mean tumor volumes after three weeks of treatment were 73 mm³ for GLV-1h164, 191 mm³ for GLV-1h100, and 422 mm³ for PBS.

"Based upon pathology, we could see that at least 60 percent of the tumors were completely regressed and the other 40 percent had very little areas of tumor cells present with a lot of necrosis, which is a sign that the tumor was responding to therapy," Gholami said in a statement.

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