Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo.

摘要: Abstract Interleukin 12 (IL-12), a disulfide-linked heterodimeric cytokine produced primarily by macrophages, is composed of light (p35) and heavy (p40) chains. It binds to receptor on T-cells natural killer cells, promoting the induction TH1 response in vitro vivo. To determine whether paracrine IL-12 secretion can alter tumor cell growth or promote antitumor immunity, we have developed delivery system using genetically engineered fibroblasts murine models. NIH3T3 cells were stably transfected express 100–240 units/106 cells/48 h expression plasmids carrying both p35 p40 genes IL-12. The effects establishment vaccination models examined poorly immunogenic melanoma line (BL-6) C57BL/6 mice. formation, nonirradiated BL-6 inoculated s.c. into mice admixed with subunits mIL-12 (3T3-IL-12) only neomycin phosphotransferase gene (3T3-Neo). Compared given injections alone, day emergence detectable tumors was significantly delayed 3T3-IL-12, but not 3T3-Neo. Effectiveness this related amount expressed 3T3-IL-12. ability locally secreted at site induce 106 irradiated mixed 3T3-IL-12 3T3-Neo injected as vaccine, challenge subsequently examined. With less than 1 × 105 significant delay noted relatively small (1.2 units/5 h). Larger amounts provided no additional therapeutic benefit. Histological examination inoculum secreting high level showed peritumoral accumulation characteristic capsule around palisades fibroblasts, decreased numbers CD4+ tumor. These results suggest that local inhibits dose dependent manner leads development an immune when indicated above. IL-12, like IL-2, -4, -6, -7 granulocytemacrophage colony-stimulating factor, against tumors. costs publication article defrayed part payment page charges. This must therefore be hereby marked advertisement accordance 18 U.S.C. Section 1734 solely indicate fact.