Published on March 15, 2007 at 5:55 PM
According to Jeronimo Cello, Ph.D., senior author of the Cancer Research paper and research assistant professor at Stony Brook, this engineering feat is like putting a double failsafe into the virus.
"The engineered poliovirus cannot produce neurovirulent copies of itself if the spacer region remains interrupted," said Cello. "And in the unlikely event that the regulatory gene element is deleted, the virus would not be able to reproduce."
To test the virus' ability to destroy neuroblastoma the researchers constructed a transgenic mouse model that allows growth of neuroblastoma cells and carries the human gene for CD155, which codes for the receptor that allows poliovirus to enter cells. The mice were then vaccinated against poliovirus.
Since most humans are immunized against poliovirus, Toyoda and his colleagues needed to know whether such immunization would interfere with the use of the virus in tumor therapy. By injecting the virus directly into the mouse tumors, the researchers demonstrated that it was possible to reach their target and still avoid interacting with the anti-poliovirus antibodies generated by the vaccine.
Not only did the poliovirus prove effective in destroying the tumors, the treatment with virus also seemed to prevent tumors from recurring. Subsequent transplanted tumors were also destroyed, presumably through an enhancement of anti-tumor immune response, say researchers. Since the poliovirus was gone from the system, however, the researchers are unsure of exactly how that immune response occurred.
"This immunity against neuroblastoma acquired by the animals is still something of a mystery, one that we hope to address in future studies," Toyoda said. "But it is an encouraging sign since neuroblastoma are known to relapse quite frequently."
The study was funded by the National Institute of Allergy and Infectious Diseases and the Stony Brook Sunrise Fund for Pediatric Cancer.