Application of interleukin-12 expressing dendritic cells for the treatment of animal model of leukemia.
Residual cancer cells appearing in blood circulation reduce the effects of radiotherapy or chemotherapy in cancer patients. It has been well documented that cultured dendritic cells can be used as a powerful tool to induce immune response. In this study, we administered different manipulations of dendritic cells (DCs), including DCs pulsed with tumor cell lysate (TCL), transfected with adenoviral IL-12 vector (AdIL-12) and transfected with AdIL-12 after being pulsed with TCL, to determine whether improved DCs based immunotherapy can specifically suppress the metastasis of tumor cells. The results demonstrated that administration of engineered DCs that transfected with AdIL-12 after being pulsed with TCL to mice with leukemia had a better protective effect than that of DCs either pulsed with TCL or transfected with AdIL-12. Moreover, depletion of CD8(+) cells in the engineered DCs administered leukemia mice reduced the protective effect. These results suggest that DCs modified with TCL and AdIL-12 can prolong survival time by enhancing the activity of cytotoxic T cells. Although more studies on the mechanisms are needed, cytokine genes engineered DCs provide a promising therapeutic potential on the murine model of leukemia.
Tsai
Bor-Yu
BY
Department of Pediatrics, National Taiwan University Hospital, No. 1, Chang-Teh Street, Taipei, Taiwan 100, Republic of China.
Lin
Yu-Li
YL
Chiang
Bor-Luen
BL
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D005818:Genetic Engineering; D007111:Immunity, Cellular / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics*; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014611:Vaccination
D018664:Interleukin-12