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Potential viral therapy weapon for difficult cancers is safe and effective in study
Date:4/22/2008

normally occurring gene was deleted and replaced with a gene that encodes an enzyme to activate chemotherapy drugs called oxazophosphorines, including cyclophosphamide (CPA). Previous studies have reported the rRp450 virus kills cancer cells by causing their cell membranes to erupt, and that the virus helps the anti-tumor effects of CPA. In the current study, rRp450/CPA treatment significantly shrunk a form of human rhabdomyosarcoma, a relatively rare and aggressive tumor that wraps around muscles and soft tissues, usually in younger children. When the grafted tumors reached 200-500mm in size, seven mice were treated twice over eight days with a combination of rRp450/CPA, with rRp450 administered by direct tumor injection 24 hours prior to CPA. The researchers noted significant tumor shrinkage with one animal perishing 20 days following initial injection, two more within 30 days, two within 40 days and the last two mice surviving nearly 50 days post treatment.

The investigators also confirmed the anti-tumor effect of rRp450 treatment alone in mouse models of human cancers rhabdomyosarcoma and neuroblastoma, where they observed significant tumor shrinkage in 13 of 13 injected tumors. Treatment with CPA alone in these models showed limited anti-tumor effectiveness. In a control group of tumor-carrying mice treated with a placebo, all died within 10 days of injection.

Also noteworthy in this study is documentation of the treatments potential safety, specifically toxicity to nerve tissues. Most research of oncolytic herpes simplex viruses (oHSVs) has so far been limited to those engineered by deleting both copies of the neurovirulence gene that prompts wild-type HSV-1 virus to spread and invade the nervous system. Deleting both copies disarms most of the virus disease-spreading properties while retaining its ability to damage targeted cancer cells. The rRp450 virus is different because it retains both copies of the virulence gene but is attenuated by d
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Contact: Nick Miller
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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