Herpes virus mutant shows potential for neuroblastoma

An attenuated form of herpes simplex virus has potent oncolytic activity in several neuroblastoma cell lines, as well as in animal models of the disease, a new study shows.

New methods of treatment for neuroblastoma, which accounts for 8% to 10% of all childhood cancers and has a survival rate below 50%, are urgently needed, Dr. Timothy P. Cripe of the University of Cincinnati College of Medicine in Ohio and colleagues note in the current online issue of Pediatric Blood and Cancer.A number of clinical trials of viruses as oncolytic therapy are underway, Dr. Cripe noted in an interview with Reuters Health, and a herpes virus simplex (HSV) 1 mutant very similar to the one used in the current study has been tested in adults. “The studies in adults suggest that these virus are safe to administer to people,” he said.In the current study, Dr. Cripe and his team investigated whether wild-type adenovirus type 5 and the HSV 1 mutant NV1066 has oncolytic activity in neuroblastoma cells.The researchers used eight different neuroblastoma cell lines in culture. While all cell lines were relatively resistant to adenovirus infection, NV1066 “was very effective in lysing all of the Nb cell lines,” Dr. Cripe and colleagues report. Further studies indicated that apoptosis was at least partially responsible for the virus’ oncolytic activity.Dr. Cripe and his team then tested the effect of intratumoral NV1066 injections in two xenograft models. Compared with controls, all of the animals injected with active virus showed significant tumor shrinkage. Animals that had tumor regrowth were given a second injection, which resulted in additional tumor shrinkage, suggesting the tumor had not acquired resistance to the virus. Microscopic studies of the injected tumor tissue found extensive necrosis.Several hurdles must be overcome before clinical trials of NV1066 are possible, Dr. Cripe told Reuters Health, not least among them the cost of producing large enough quantities of the biological agent. He said he is talking to industry and government about funding to move the research forward.Clinical studies of the virus in neuroblastoma would likely begin with direct injections into the tumors, he added, with the hope that the virus could eventually be administered systemically to treat metastatic disease. Unpublished animal research by his team suggests such a method could be effective, Dr. Cripe said.”There’s a lot of reason for hope, but these are only some of the initial steps,” he concluded.(Source: Pediatric Blood Cancer, Reuters Health, December 2004)