Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4328-4335
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
Shin-ichiro Fujii,
Hirofumi Hamada,
Koji Fujimoto,
Taizo Shimomura, and
Makoto Kawakita
From the Center for Bone Marrow Transplantation and Immunotherapy,
Institute for Clinical Research, Kumamoto National Hospital, Kumamoto,
Japan; the Department of Molecular Biotherapy Research, Cancer
Chemotherapy Center, Cancer Institute, Tokyo, Japan; and the Second
Department of Internal Medicine, Kumamoto University School of
Medicine, Kumamoto, Japan.
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 
(TNF) 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.
