High cytokine production and effective antitumor activity of a recombinant vaccinia virus encoding murine interleukin 12.
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 micrograms/10(6) cells/24 h) of biologically active mIL-12. Mice injected s.c. with 10(6) 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.
Meko
J B
JB
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Yim
J H
JH
Tsung
K
K
Norton
J A
JA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy* / Q000821:virology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics* / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology
D046911:Macromolecular Substances; D011994:Recombinant Proteins; D014764:Viral Proteins; D018664:Interleukin-12