[Augmentation of vaccination effects of PGE2-producing tumor cells by transfection with cytokine genes].
Potentially antigenic tumors often escape from the immune surveillance system by producing immunosuppressive factors. It has previously been reported that a progressor-type murine fibrosarcoma culture line, QRpP cells, produced high levels of PGE2 compared with a regressor-type tumor line, QR-32 cells, and that QRpP cells progressively grew in syngeneic C57BL/6 mice. In order to improve suppressed immunogenicity of QRpP cells with the high levels of PGE2, the author transfected QRpP cells with an effective expression vector containing cDNA for IL-2, IFN-gamma and TNF-alpha. These transfected clones expressed mRNA for IL-2, IFN-gamma and TNF-alpha, respectively, and produced high levels of cytokines in their culture supernatants. Consequentry, QRpP cells transfected with IL-2 (QRpP-IL-2), IFN-gamma (QRpP-IFN-gamma), IL-2 and IFN-gamma (QRpP-IL-2/IFN-gamma), TNF-alpha (QRpP-TNF-alpha) lowered in tumorigenicity. In particular, the mice that had rejected the implantation of QRpP-IL-2 clone also rejected implantation of the parental QRpP cells. The activity of pre-cytotoxic T cells (pre-CTLs) obtained from the mice implanted with QRpP-IL-2 clone was higher than that of the mice implanted with other transfectants. These results suggested that transfection with the gene for IL-2 is an effective strategy against the producing immunosuppressive factors such as PGE2.
Ohiro
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Y
Second Department of Oral Surgery, Hokkaido University School of Dentistry, Sapporo, Japan.
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014611:Vaccination; D014612:Vaccines
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D007371:Interferon-gamma; D015232:Dinoprostone