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Genetically reprogrammed HSV given systemically shrinks distant sarcomas
Date:7/7/2010

take in cancer cells.

The rRp450 oncolytic virus used in the study was derived from herpes simplex type 1. The virus was genetically modified by scientists by removing a gene that makes the virus unable to replicate efficiently in dormant cells. This causes the virus to selectively target and replicate in rapidly growing cancer cells while leaving normally dormant healthy tissue cells alone.

After removing the one gene from the virus, researchers replaced it with a gene that encodes an enzyme that activates a class of anti-tumor chemotherapies called oxazaphosphorines. The overall therapeutic approach is for the virus to infect and degrade the cancer cells and then activate chemotherapy agents as anti-angiogenic agents cut off vascular growth and blood supply to the tumors.

In the current study, however, researchers treated the mice only with rRp450 and the anti-angiogenic drug bevacizumab. This allowed them to test whether the virus could be given systemically, how anti-angiogenic drugs affected virus tumor uptake and the impact this had on tumor growth.

In mice receiving bevacizumab prior to the rRp450, overall tumor shrinkage averaged 40 percent. In mice receiving rRp450 before bevacizumab, tumor size was reduced by an average of 75 percent. The researchers also reported that mice treated with rRp450 before bevacizumab had longer survival rates.

Results of the current study could be used immediately to help design subsequent research into treatment protocols for oncolytic viruses, particularly clinical trials involving combination therapeutic strategies, Dr. Cripe said. Clinical trials are underway in the United States and Europe using oncolytic herpes viruses similar to the one used in the current study.


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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert  

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