Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors
Technical Report,01 Sep 2011,31 Aug 2015
University of Alabama at Birmingham Birmingham United States
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Many patients with neurofibromatosis type I NF-1 will develop tumors in their peripheral nerves that progress to a cancer called a malignant peripheral nerve sheath tumor or MPNST. These tumors grow progressively and if they cannot be completely removed surgically, they are eventually fatal. Radiation provides some benefit but is mostly ineffective and there are no proven chemotherapies or medicines that will prevent the progressive growth of these tumors. We have been working with genetically engineered human herpes simplex virus HSV as a means of treating nervous system tumors. We have genetically modified these viruses to make them safe and unable to grow in normal cells, but that can grow in tumor cells causing them to die, a process called oncolysis tumorlysis. In addition, we have inserted genes in these viruses that allow them to overcome different mechanisms that tumor cells have to prevent virus growth. Our objective is to determine how effectively MPNST cells can be infected and killed by our engineered HSVs. We will test our panel of viruses against a panel of MPNST-derived cells. We will examine the molecular features of the tumor cells to identify similarities which reflect a tumor cells response to oHSV.