Anti-cancer activity of the HIV accessory molecule viral protein R (Vpr): Delivery as a DNA expression plasmid or biologically active peptides.

By virtue of its ability to induce cell cycle arrest and apoptosis, the HIV accessory protein Vpr (viral protein R) has been evaluated by us and others as an anti-proliferative/anti-cancer agent. We have demonstrated that Vpr, when delivered to established experimental B16.F10 melanoma tumors in mice as a DNA expression plasmid through in vivo electroporation, can result in complete regression of the established tumors. We have also demonstrated that Vpr peptides from the carboxy region of the protein can inhibit in vitro growth of both B16.F10 melanoma as well as human HeLa cervical carcinoma tumor cells. These findings, summarized in this report, underscore the potential of Vpr as an anti-cancer agent and warrants, we believe, further experimental as well as clinical evaluation.

Analysis of the potential for HIV-1 Vpr as an anti-cancer agent.

Viral protein R (Vpr) is a 14kD, 96 amino acid accessory protein of the HIV virion that has been demonstrated to have important functions in the viral replication cycle including, among others, the induction of cell cycle arrest and apoptosis in rapidly proliferating cells, which results in immune dysfunction in infected individuals. Several investigators have studied the potential use of the apoptosis inducing and cell cycle arrest effect of Vpr as an anti-tumor therapeutic. In vitro studies have indicated that Vpr is cytotoxic against a large number of different tumor cell types including a number that are p53 independent. Likewise, some in vivo tumor studies using different delivery platforms/methods have indicated an anti-cancer effect mediated by Vpr. Our group has used the aggressive and poorly immunogenic murine melanoma tumor line B16.F10 as a model to deliver, through in vivo electroporation, Vpr expressing plasmids to established tumors and have demonstrated that this treatment regimen can induce growth attenuation and tumor regression in a proportion of the treated mice and appears to be associated with the induction of intratumoral apoptosis. Overall, to date, the data from a number of research groups, including our own, have indicated that Vpr has biological activity against a number of tumors in both in vivo and in vitro models and, as such, may be a potential candidate for testing in human clinical trials. In this report, we summarize the evidence supporting this hypothesis.