Treatment of experimental subcutaneous human melanoma with a replication-restricted herpes simplex virus mutant.
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-1716 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.
Randazzo
B P
BP
The Wistar Institute, Department of Dermatology, University of Pennsylvania Medical System, Philadelphia 19104, USA.
Bhat
M G
MG
Kesari
S
S
Fraser
N W
NW
Brown
S M
SM
D000704:Analysis of Variance; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D016923:Cell Death / Q000502:physiology; D004279:DNA, Viral / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000473:pathology / Q000628:therapy* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009365:Neoplasm Regression, Spontaneous / Q000473:pathology; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000956:Antigens, Viral; D004279:DNA, Viral