Potential viral therapy weapon for difficult cancers is safe and effectiv... (eletion of a different gene. Earlier pre...)

Potential viral therapy weapon for difficult cancers is safe and effective in study

Date:4/22/2008

eletion of a different gene. Earlier preclinical studies showed that deleting just the single gene increases rRp450s ability to degrade cancer cells, but until the current study little had been known about whether a virus with a single-gene mutation would retain neural toxicity to the recipient.

Dr. Cripe and his colleagues addressed the neural toxicity question in part by injecting normal human liver, skin and nerve sheath cells grown in the laboratory with the rRp450 virus and with the normal wild-type HSV-1 virus. Over a 72-hour period, researchers noted a robust replication of the wild-type HSV-1 in these cells, but in cells injected with rRp450, the replication rate was inhibited 10,000 fold with no signs of productive virus infection.

Researchers also tested wild-type HSV-1 in mice by intravenous and intracerebral (brain) injection, comparing those results to mice injected initially with rRp450 and with CPA 24 hours later. Mice getting the wild-type virus suffered from high infection rates, abnormal gait and in some cases death. In contrast, mice receiving a combination of rRp450/CPA tolerated the treatment well with no significant clinical effects on their blood counts or chemistries. The researchers did note that tissue samples tested during the study retained some viral genetic material, notably DNA fragments, although there were no signs of active disease. Because mice received combined rRp450/CPA only once during the toxicity part of the study, safety tests based on repeated dosing are still needed, and would be necessary to support a multi-dose clinical trial, the researchers said.

Based on these findings and other preclinical studies, we expect oncolytic viral therapy will be one additional treatment modality available in the future for oncologists, Dr. Cripe said. The challenge over the next decade will be determining which viruses work best for which cancers, at what doses, schedules, routes of administration, and in w
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Contact: Nick Miller
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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