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Nonreplicating Virus Kills Leukemia in Mouse and Culture Models

By BiotechDaily International staff writers
Posted on 27 Aug 2013
Image: Electron micrograph depicts the rhabdovirus responsible for vesicular stomatitis (VS) in horses, cattle, and pigs. An inactivated rhabdovirus was used in recent studies to destroy leukemia cells (Photo couryesy of the [US] Centers for Disease Control (CDC)).
Image: Electron micrograph depicts the rhabdovirus responsible for vesicular stomatitis (VS) in horses, cattle, and pigs. An inactivated rhabdovirus was used in recent studies to destroy leukemia cells (Photo couryesy of the [US] Centers for Disease Control (CDC)).
A biopharmaceutical drug comprising nonreplicating virus particles killed leukemia cells in a mouse leukemia model and in cultures of cells taken from patients with multiple drug resistant forms of the disease.

Investigators at the University of Ottawa (Canada) speculated that high doses on a nonreplicating virus would be able to kill blood cancer cells without the dangers inherent in the use of fully competent live viruses. Toward this end they developed a method based on attenuation with UV light to produce unique high-titer bioactive yet nonreplicating rhabdovirus-derived particles (NRRPs).

This novel NRRP bio-drug was shown in a paper published in the July 12, 2013, online edition of Blood Cancer Journal to possess direct cytolytic and immunomodulatory activity against acute leukemia. In a mouse model of leukemia treated with the NRRPs 80% of the mice had markedly prolonged survival and 60% were eventually cured of the disease, while all of the untreated mice died of leukemia within 20 days.

In laboratory cultures, NRRP resistance in normal cells was mediated by intact antiviral defenses including interferon (IFN). In contrast, NRRPs administered cell cultures derived from clinical samples obtained from patients with high-burden multidrug-resistant acute myeloid leukemia killed the cancer cells.

"Our research indicated that a replicating virus might not be the safest or most effective approach for treating leukemia, so we decided to investigate whether we could make virus-derived particles that no longer replicate but still kill cancer," said senior author Dr. David Conrad, a doctor candidate in cellular and molecular medicine at the University of Ottawa. "We were delighted to see that this novel therapy was very safe at high doses, and worked extremely well in our laboratory leukemia models. We hope to test this in patients in the near future."

"Leukemia is a devastating disease that can be very difficult to treat, and new therapies are urgently needed," said Dr. Conrad. "While we are still at the early stages of this research, I think this therapy holds a lot of promise because it appears to have a potent, long-lasting effect on leukemia without the debilitating side effects of many cancer therapies used in the clinic right now. We will likely see even better results once we optimize the dose in our preparations to advance this research into human clinical trials."

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