Antiangiogenic Drug Enhances Systemic Oncolytic Herpes Virus Treatment of Disseminated Sarcoma

A study found that treatment of metastatic cancer with a genetically engineered oncolytic virus can be augmented by antiangiogenic drugs, but only if administered in the proper sequence.

Investigators at the Cincinnati Children's Hospital Medical Center (OH, USA) worked with the oncolytic virus rRp450, which is a genetically engineered form of herpes simplex virus type 1. The virus had been modified by removing a specific gene so that the virus was then unable to replicate efficiently in dormant cells. This causes the virus to selectively target and replicate in rapidly growing cancer cells while failing to infect dormant healthy cells. The virus was further modified by the addition of a gene that encodes an enzyme that activates a class of antitumor agents called oxazaphosphorines.

In the current study, the investigators treated mice with disseminated sarcomas systemically with rRp450 to attack tumors via the blood stream instead of being injected directly into tumors. The oncolytic virus was administered either before or after treatment with the antiangiogenic drug bevacizumab.

Results published in the May 28, 2010, online edition of the journal Gene Therapy revealed that tumors in mice receiving bevacizumab prior to the rRp450 shrank an average of 40%, while the tumors in mice receiving rRp450 before bevacizumab shrank by an average of 75%. Furthermore, mice treated with rRp450 before bevacizumab had longer survival rates.

"Systemic biodistribution has been a major stumbling block for using virus vectors in gene transfer and virotherapy to treat cancer, but we show that viruses can be used systemically by giving them intravenously to get an antitumor effect,” said senior author Dr. Timothy Cripe, professor of hematology and oncology at Cincinnati Children's Hospital Medical Center. "Our data suggest that i.v. oncolytic herpes simplex virus can treat distant sites of disease and can be enhanced by antiangiogenic therapy, but only when given in the proper sequence.”

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Cincinnati Children's Hospital Medical Center