Antitumor effects of fusions composed of dendritic cells and fibroblasts transfected with genomic DNA from tumor cells.
Based on several previous studies indicating that transfection of genomic DNA can stably alter the character of the cells that take up the exogenous DNA, we investigated antitumor immunity conferred by fusions of syngeneic dendritic cells (DCs) and allogeneic fibroblasts (NIH3T3) transfected with genomic DNA from B16 tumor cells. Fusion cells (FCs) composed of dendritic and genetically engineered NIH3T3 cells were prepared with polyethylene glycol, and fusion efficiency was 30.3%. Prior immunization with FCs prevented tumor formation upon challenge with B16 tumor cells. Efficacy was reduced when studies were performed in mice depleted of NK cells. Vaccination with FCs containing DCs and fibroblasts transfected with denatured DNA did not inhibit tumor growth. Cytotoxic T cell (CTL) activity of spleen cells from immunized mice against both Yac-1 and tumor cells was also stimulated by administration of FCs compared with the activity observed for cells obtained from naïve mice. These data demonstrate the therapeutic efficacy of fusion cell-based vaccine therapy using syngeneic DCs and allogeneic fibroblasts transfected with tumor-derived genomic DNA.
Nakamura
Motoyuki
M
Department of Oncology, Institute of DNA Medicine, Jikei University, 3-25-8 Nishishinbashi, Minato-ku, 105-8461, Tokyo, Japan.
Kikuchi
Tetsuro
T
Kufe
Donald W
DW
Ohno
Tsuneya
T
D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000235:genetics*; D003713:Dendritic Cells / Q000502:physiology*; D007114:Immunization; D007167:Immunotherapy; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells / Q000502:physiology*; D011092:Polyethylene Glycols / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D004273:DNA, Neoplasm; D011092:Polyethylene Glycols