RESUMEN
A novel approach for a dentritic cells (DCs)-based tumor vaccine was developed for the formation of hybrid-engineered J558 after fusion with DCs. To make the hybrid-tumor vaccine generate more efficient specific CTL cytotoxicity against wild-type tumor cells, we genetically engineered tumor cells with mIL-12 gene prior to the cell fusion. mIL-12 was detected at 870 +/- 60 pg/(10(5) cells/ml) in the culture supernatants and the fusion ratio was about 30% by the co-focal microscopic analysis. Vaccination of mice with DCs fused with engineered J558 induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo. These results suggest that this approach of using DCs fused with engineered tumor cells could be applied in clinical settings of DCs-based cancer vaccines.
Asunto(s)
Animales , Femenino , Ratones , Vacunas contra el Cáncer , Alergia e Inmunología , Fusión Celular , Línea Celular Tumoral , Células Dendríticas , Alergia e Inmunología , Metabolismo , Técnicas de Transferencia de Gen , Células Híbridas , Linfoma de Células B , Genética , Alergia e Inmunología , Patología , Ratones Endogámicos BALB C , Mieloma Múltiple , Genética , Alergia e Inmunología , Patología , Linfocitos T Citotóxicos , Alergia e Inmunología , Transfección , Vacunas de ADN , Alergia e InmunologíaRESUMEN
<p><b>OBJECTIVE</b>To study the antitumor activity of engineered fusion of tumor cell and dendritic cells (DC).</p><p><b>METHODS</b>J558 tumor cells were transfected with mouse IL-12 (mIL-12) gene and then fused with DCs to develop a hybrid-engineered tumor vaccine. BALB/c mice were challenged with wild-type J558 tumor cells 14 days after vaccinated with hybrid-engineered J558.</p><p><b>RESULTS</b>mIL-12 was detected at (870 +/- 60) pg.(10(5) cells)(-1).ml(-1) in the culture supernatants and the cell-fusion rate was about 30% by co-focal microscopy. In addition, the lymphocytes from popliteal nodes and groin nodes of these mice vaccinated with hybrid-engineered J558 secreted higher levels of IFN-gamma than that of other control mice, and vaccination of mice with the fusion vaccine induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo.</p><p><b>CONCLUSION</b>It suggested that vaccination of mice with the fusion vaccine induced stronger Th1-dominant responses and this approach could perhaps be applied to clinical settings of DCs-based cancer vaccines.</p>