Replicating herpes simplex virus vectors for cancer gene therapy

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Abstract
Attenuated viral vectors based on herpes simplex virus (HSV) are capable of killing cancer cells directly while sparing normal tissue in animal models of disease. This selective ability is likely due to the evolutionary constraints on the virus to establish lifelong infection in its host without causing destruction of normal tissues. However, extensive experimental animal data show that cancer cells are able to sustain a productive viral infection, which ultimately leads to cell death and tumour regression. Moreover, preliminary results generated in two Phase I clinical studies of modified replicating HSV for the treatment of brain tumours (e.g., glioblastoma multiforme) have been encouraging and suggest that the safety data generated in animals are predictive of human safety. Although much progress has been made in developing oncolytic HSV vectors for clinical use, there is still a long way to go to determine which combinations of virus, surgery, radiation and chemotherapy will provide improved therapy for the control and eradication of a variety of human cancers.