Chemo Drug and Virus Work Together

Cytoxan, a chemotherapy drug, helps a virus used against incurable brain tumors work better, say U.S. researchers.

Researchers at the Arthur G. James Cancer Hospital in Ohio discovered that when herpes simplex virus was injected directly into brain tumors in rats, it entered only the cancer cells and killed them.

Unfortunately, within hours of the injection, natural killer cells (NKs) and macrophages from the immune system showed up to destroy the virus, limiting the treatment’s effectiveness.

The team pretreated the rats with a variety of drugs to stop this phenomenon, and found that Cytoxan (cyclophosphamide) inhibited the early immune response and let the virus do its work, but did not totally suppress the immune system.

The drug not only reduced the number of NKs and macrophages, but stopped NKs from making interferon gamma (IFNg), which draws immune cells to infection sites.

Rats with brain tumors that were given the virus, but not the drug had three times the number of macrophages in their brains and 10 times more IFNg than they did before within a few hours of the injection.

After 72 hours, IFNg levels had risen 120-fold. Rats that were pretreated with Cytoxan had only half as many NKs and macrophages and only a slight rise in their IFNg levels at the same time points.

The research appears in the August 22 issue of the Proceedings of the National Academies of Science.