PMID- 10361131 OWN - NLM STAT- MEDLINE DCOM- 19990701 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 93 IP - 12 DP - 1999 Jun 15 TI - Activated dendritic cells from bone marrow cells of mice receiving cytokine-expressing tumor cells are associated with the enhanced survival of mice bearing syngeneic tumors. PG - 4328-35 AB - Dendritic cells (DCs), which phagocytose antigens and subsequently proliferate and migrate, may be the most powerful antigen-presenting cells that activate naive T cells. To determine their role in the immune response to tumors, we used WEHI-3B murine leukemia cells transduced with adenovirus vectors expressing cytokines. We found that mixtures of irradiated cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) plus those expressing interleukin-4 (IL-4) or tumor necrosis factor alpha (TNFalpha) protected mice against WEHI-3B-induced leukemias. When bone marrow mononuclear cells (BMMNCs) obtained from mice that had been injected with irradiated, cytokine-expressing tumor cells were injected into tumor-bearing mice, the survival of the latter was significantly prolonged; the longest survival was observed in mice receiving BMMNCs containing an increased number of DCs from animals injected with a mixture of tumor cells expressing GM-CSF with those expressing IL-4. Assay for antileukemic effects in spleen of the latter animals showed specific antitumor cytotoxicity against WEHI-3B, suggesting that DCs from donor mice activate specific T cells in the tumor-bearing recipients. These results suggest that the infusion of syngeneic BMMNCs stimulated with cytokine-expressing tumor cells may be effective in treating certain types of tumors. FAU - Fujii, S AU - Fujii S AD - Center for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, Kumamoto, Japan. FAU - Hamada, H AU - Hamada H FAU - Fujimoto, K AU - Fujimoto K FAU - Shimomura, T AU - Shimomura T FAU - Kawakita, M AU - Kawakita M LA - eng PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Bone Marrow Cells/*immunology MH - Cancer Vaccines MH - Cricetinae MH - Cytokines/*genetics/*immunology MH - Dendritic Cells/*immunology MH - *Gene Expression MH - Genetic Vectors MH - Granulocyte-Macrophage Colony-Stimulating Factor/genetics/immunology MH - *Immunotherapy MH - Interleukin-4/genetics/immunology MH - Leukemia, Experimental/immunology/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Rats MH - Transfection MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/genetics/immunology EDAT- 1999/06/11 00:00 MHDA- 1999/06/11 00:01 CRDT- 1999/06/11 00:00 PHST- 1999/06/11 00:00 [pubmed] PHST- 1999/06/11 00:01 [medline] PHST- 1999/06/11 00:00 [entrez] AID - S0006-4971(20)59463-9 [pii] PST - ppublish SO - Blood. 1999 Jun 15;93(12):4328-35.