Original Article

Journal of Investigative Dermatology (1997) 108, 933–937; doi:10.1111/1523-1747.ep12295238

Treatment of Experimental Subcutaneous Human Melanoma with a Replication-Restricted Herpes Simplex Virus Mutant

Bruce P Randazzo1,2, Mulki G Bhat3, Santosh Kesari1,3, Nigel W Fraser1 and S Moira Brown4

  1. 1The Wistar Institute, Philadelphia, Pennsylvania, U.S.A.
  2. 2Department of Dermatology, University of Pennsylvania Medical System, Philadelphia, Pennsylvania, U.S.A.
  3. 3School of Medicine, University of Pennsylvania Medical System, Philadelphia, Pennsylvania, U.S.A.
  4. 4Glasgow University, Neurovirology Research Laboratories, Glasgow, Scotland

Received 26 July 1996; Revised 3 February 1997; Accepted 28 February 1997.

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Abstract

Modified, non-neurovirulent herpes simplex viruses (HSV) have shown promise for the treatment of brain tumors, including intracranial melanoma. In this report, we show that HSV-1716, an HSV-1 mutant lacking both copies of the gene coding-infected cell protein 34.5 (ICP 34.5), can effectively treat experimental subcutaneous human melanoma in mice. In vitro, HSV-1716 replicated in all 26 human melanoma cell lines tested, efficiently lysing the cells. Therapeutic infection of subcutaneous human melanoma nodules with HSV-.171.6 led to viral replication that was restricted to tumor cells by immunohistochemistry. Moreover, HSV-1716 treatment significantly inhibited progression of preformed subcutaneous human melanoma nodules in SCID mice and caused complete regression of some tumors. This work expands the potential scope of HSV-1-based cancer therapy.

Keywords:

experimental neoplasm, HSV-1, ICP-34.5

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