Molecular Therapy
Volume 2, Issue 4, October 2000, Pages 324-329
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Article
Tumor Growth Inhibition by Intratumoral Inoculation of Defective Herpes Simplex Virus Vectors Expressing Granulocyte–Macrophage Colony-Stimulating Factor

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To evaluate the potential of defective herpes simplex virus (HSV) amplicon vectors as in vivo cytokine gene transfer vehicles for active immunotherapy, we generated a defective HSV vector that encodes the murine granulocyte–macrophage colony-stimulating factor (GM-CSF) gene, using a replication-defective HSV as helper virus. A variety of murine tumor cell lines were efficiently infected in vitro with the defective GM-CSF vector (dvGM), and this led to the synthesis and secretion of murine GM-CSF. In an established bilateral subcutaneous tumor model with Harding–Passey murine melanoma, unilateral intratumoral inoculation of dvGM significantly inhibited tumor growth of both the inoculated and noninoculated contralateral tumors. This tumor inhibition was dose-dependent and resulted in increased survival of the dvGM-treated mice. Inoculation of a lacZ-expressing defective vector had no effect on tumor growth. We conclude that this defective HSV vector system offers an effective method for cytokine gene delivery in vivo and that GM-CSF expression in tumors has antitumor activity.

Keywords

herpes simplex virus
GM-CSF
melanoma
cancer therapy
Harding–Passey

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