Novel
therapies and delivery methods directed against
malignancies such as
melanoma, and particularly metastatic
melanoma, are needed. The HIV-1 accessory
protein Vpr (
viral protein R) has previously been demonstrated to induce G2 cell cycle arrest as well as in vitro growth inhibition/killing of a number of
tumor cells by apoptosis. In vivo electroporation has been utilized as an effective delivery method for pharmacologic agents and
DNA plasmids that express "therapeutic"
proteins and has been targeted to various tissues, including malignant
tumors. For the study reported here, we hypothesized that intratumoral delivery of a Vpr expression plasmid through in vivo electroporation would induce apoptosis and growth attenuation or regression of
melanoma tumors. Established subcutaneous B16.F10
melanoma tumors were injected intratumorally with a Vpr-expressing (either 25 or 100 microg) plasmid, followed by electroporation, on day 0 (i.e., when
tumors had attained an appropriate size) and day 4. Treatment with 25 or 100 microg of the Vpr-expressing plasmid resulted in complete
tumor regression with long-term survival in 14.3 and 7.1% of the mice, respectively. In addition, electroporative delivery of the Vpr-expressing plasmid was shown to induce apoptosis in
tumors after intratumoral injection. This is the first report demonstrating the ability of Vpr, when delivered as
a DNA expression plasmid with in vivo electroporation, to attenuate
melanoma lesion growth and induce complete
tumor regression coupled with long-term survival of mice in a highly aggressive and metastatic solid
tumor model.