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Researchers Say Targeted Virus Kills Cancer Cells

Posted on: Thursday, 4 May 2006, 06:01 CDT

According to researchers at The University of Texas MD Anderson Cancer Center, an engineered virus tracks down and infects the most common and deadly form of brain cancer and then kills tumor cells by forcing them to devour themselves.

According to the researchers, who reported their findings in the Journal of the National Cancer Institute, the modified adenovirus homed in on malignant glioma cells in mice and induced enough self-cannibalization among the cancer cells - a process called autophagy - to reduce tumor size and extend survival.

"This virus uses telomerase, an enzyme found in 80% of brain tumors, as a target," explained senior author Dr Seiji Kondo, associate professor in the department of neurosurgery at MD Anderson. "Once the virus enters the cell, it needs telomerase to replicate. Normal brain tissue does not have telomerase, so this virus replicates only in cancer cells."

Other cancers are telomerase-positive, and the researchers showed in lab experiments that the virus kills human prostate and human cervical cancer cells while sparing normal tissue.

In addition to demonstrating the therapeutic potential of the virus, called hTERT-Ad, Dr Kondo says the international research team also clarified the mechanism by which such conditionally replicating adenoviruses (CRAs) infect and kill cancer cells.

Autophagy is a protective process that cells employ to consume part of themselves when nutrients are scarce or to destroy some of their organelles to recycle their components. A double membrane forms around the material to be consumed, then everything inside is digested.

Dr Kondo and colleagues showed that hTERT-Ad infected the glioma cells and induced autophagy by inactivating a molecular pathway - the mammalian target of rapamycin (mTOR) pathway - that is known to prevent cellular self-cannibalization.

The result was a huge difference in tumor volume among mice with subcutaneous malignant glioma that got hTERT-Ad and those that received a different, non-replicating virus. Average tumor size in the hTERT-Ad group was 39 cubic millimeters, while those receiving the other virus had an average tumor volume of 200 cubic millimeters.

Among mice with malignant gliomas in the brain, those treated with three injections of hTERT-Ad on average lived 53 days. Those receiving the control adenoviruses lived on average 29 days. Two of the hTERT-Ad mice survived 60 days and had no detectable brain tumors.

To improve cancer therapeutics, Dr Kondo and colleagues concluded that it is vital to identify molecules that regulate autophagy in cancer cells and to understand how autophagy is associated with cell death, a relatively new field in cancer research.

The research group is following up the malignant glioma findings by studying ways to improve the efficiency of viral infection of cancer cells.

Source: Datamonitor

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