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Anticancer Effect of a Lentiviral Vector Capable of Expressing HIV-1 Vpr

School of Dentistry [S. P., M. K. K., D. Y., A. L., B. L., N-H. P.], Dental Research Institute [S. P., M. K. K., D. Y., A. L., N-H. P.], School of Medicine Department of Microbiology and Immunology [S. K., B. P., I. S. Y. C.], and AIDS Institute [S. K., B. P., I. S. Y. C.], University of California Los Angeles, Los Angeles, California 90095-1668

A lentiviral vector capable of expressing the HIV-1 vpr gene (Vpr lentiviral vector) was constructed, and its in vivo anticancer effect was determined against cutaneous tumors derived from the AT-84 oral cancer cells in immunocompetent mice. A single intratumoral injection of the Vpr lentiviral vector not only significantly reduced the primary tumor volume but also completely regressed tumors in >40% of animals. More interestingly, the mice of which the primary tumors were completely regressed by the Vpr lentiviral vector were additionally protected from a secondary challenge of AT-84 cells. These data suggest that the Vpr lentiviral vector elicits its anticancer activity in part by the activation of the immune system. The above suggestion is additionally supported by the failure of the lentiviral vector to demonstrate anticancer activity in immunocompromised nude or SCID mice. The Vpr lentiviral vector offers a powerful new strategy for cancer gene therapy and may be useful for the control of solid tumors, such as human oral squamous cell carcinomas.

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