In this study, one of Chiocca's fellows, Giulia Fulci, now at Massachusetts General Hospital in Boston , examined brains from rats treated with the virus, with and without the drug to identify the immune cells present in the tumor before injection of the virus, and at different times afterward.
Six hours after the injection of the virus, she found that high numbers of NK cells, macrophages and brain-tissue immune cells called microglia had moved into the tumor. The number of macrophages, for example, had risen three fold. In animals given the drug, on the other hand, the number of these immune cells increased by only one half.
Other experiments performed together with Michael A. Caligiuri, director of the OSU Comprehensive Cancer Center , revealed that when the drug is added to NK cells growing in the laboratory, the cells stop making an immune substance called interferon gamma (IFNg). One key effect of IFNg is to attract immune cells to an infection site. The production of the substance could therefore intensify the immune response against the anti-cancer virus.
Furthermore the researchers found that in rat brain tumors treated with the virus but not with the drug, IFNg levels rose by 10 times after six hours and by more than 120 times after 72 hours. Animals given the drug showed only small increases of IFNg.
Lastly, the researchers tested the treatment in brain tumors in mice that cannot make IFNg. They found that viral genes were expressed much more in these animals.
Overall, the study suggests that cyclophosphamide improves the cancer-killing ability of this virus by inhibiting the activity of NK cells and certain other immune cells and by blocking the ability of cells to make IFNg.
"Over the past decade, cancer-killing viruses have been tested in people as a treatment for cancers of the pancreas and lun
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University
29-Aug-2006