Targeted Virus Compels Cancer Cells to Eat Themselves

Reprogramming the brain of brain
killers: adenovirus hTERT-Ad
© NCI Visuals Online

The modified adenovirus homed in on malignant glioma cells in mice and induced enough self-cannibalisation among the cancer cells - a process called autophagy - to reduce tumour size and extend survival, says senior author Seiji Kondo, M.D., Ph.D., associate professor in the Department of Neurosurgery at M. D. Anderson Cancer Center run by the University of Texas.

"This virus uses telomerase, an enzyme found in 80 percent of brain tumours, as a target," Kondo says. "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." The research showed in lab experiments that the virus kills human prostate and human cervical cancer cells while sparing normal tissue.

Demonstrating the therapeutic potential of the virus, called hTERT-Ad, Kondo says the international research team also clarified the mechanism by which such conditionally replicating adenoviruses infect and kill cancer cells. Kondo and colleagues could show that hTERT-Ad infected the glioma cells and induced autophagy by inactivating a molecular pathway that is known to prevent cellular self-cannibalisation.

The result was a difference in tumour volume among mice with subcutaneous malignant glioma that got hTERT-Ad and those that received a different, non-replicating virus. Average tumour size in the hTERT-Ad group was 39 cubic millimeters, while those receiving the other virus had an average tumour 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 tumours.; Source: University of Texas M. D. Anderson Cancer Center