Virotherapy on Primary Neuroblastoma Cells

After brain cancer, the most common solid tumor in children is neuroblastoma. Some versions of neuroblastoma are highly deadly, with fewer than half of patients cured despite surgery, radiation, high dose chemotherapy, bone marrow transplantation, and treatment with vitamin A forms that cause cells to mature and stop dividing. It is widely believed by most pediatric hematologists/oncologists that we have reached a plateau in our use of these treatments, and further refinements will only bring minimal improvements in increasing patient survival. A new theory about why cancers return, even years after treatment, is that a small number of cells are the real 'seeds' of the cancer, known as cancer stem cells or tumor initiating cells, and these cells are relatively resistant to conventional therapies. Thus, not only are new therapeutic strategies desperately needed for neuroblastoma, but such approaches should kill these resistant cells. A promising new avenue of therapy is the use of viruses to selectively infect and kill cancer cells, and several clinical trials have been conducted using safe versions of Herpes simplex virus. We found that some neuroblastoma stem cells are susceptible to infection with these viruses, suggesting this type of treatment might be beneficial in preventing relapse. Here we propose to determine which versions of the virus are the best at killing neuroblastoma stem cells, and to isolate new viruses that work even better. This project will guide the choice of agents for use in clinical trials and may result in newly enhanced therapeutic agent for neuroblastoma.