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High Cytokine Production and Effective Antitumor Activity of a Recombinant Vaccinia Virus Encoding Murine Interleukin 12¹

Laboratory of Biological Therapy, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110

We have constructed a recombinant vaccinia virus (recVV), vKT0334 mIL-12, containing the genes encoding the p35 and p40 subunits of murine interleukin-12 (mIL-12). In vitro experiments demonstrated that vKT0334 mIL-12 efficiently infected a variety of murine and human tumor cell lines and produced very high amounts (1.5 µg/10⁶ cells/24 h) of biologically active mIL-12. Mice injected s.c. with 10⁶ MCA 105 sarcoma cells, followed by injection at the same site with saline or a control recVV, vKT033, containing no mIL-12 genes, all developed progressively growing tumor, whereas 60% of animals injected with vKT0334 mIL-12 remained tumor free (P < 0.0005). Furthermore, tumor growth was significantly reduced in the remaining mice treated with vKT0334 mIL-12 that did develop tumor compared with mice treated with vKT033 (P < 0.03) or saline (P < 0.0001). We conclude that recVV expressing high levels of mIL-12 offers an effective in vivo method of cytokine gene delivery and expression in tumors with subsequent antitumor effect.

¹ This study was supported by NIH Grant 5T32 CA-09621.

² To whom requests for reprints should be addressed, at Department of Surgery, Washington University School of Medicine, One Barnes Hospital Plaza, 5108 Queeny Tower, St. Louis, MO 63110. Phone: (314) 362-7320; Fax: (314) 454-3056.

Received 7/17/95. Accepted 9/13/95.

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