| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Research Abstract |
Dendritic cells (DC) are special subsets of antigen presenting cells (APC) characterized by their strong abilities to induce acquired immunity including anti-tumor immunity and by their weak abilities to directly (i.e., cytotoxic capability) and/or indirectly (via ADCC) kill harmful cells (e.g., tumor cells). Conversely, macrophages (mΦ) serve as weak APC and cells possessing ADCC. Our hypothesis was that DC-mΦ hybrids may overcome each weakness and exert beneficial and strong anti-tumor immunity. To test this hypothesis, we first established a new strategy to select only hybrid cells by our double-selection method. Second, using this selection method, we fused DC and mΦ, and then established hybrids were examined for their phenotypes. We found difficulties to distinguish these two cell types by functional and surface phenotypes and also found heterogeneity between hybrid clones (Matsue H, et al., Cancer Biology & Therapy, 3:1145-1151, 2004). During a series of hybrid experiments, we r
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ealized that DC were activated by cell fusion at extremely high cell density. We shifted our research focus to figure out the reason for their activation and found that DC are activated via gap junctions during cell fusion. As a by-product of this project, we discovered that gap junction-mediated intercellular communication (GJIC) between DC is required for effective activation of DC. (Matsue H, et al., J Immunol. 176:181-190, 2006). We believe that harness of GJIC between DC may become a new strategy to induce or silence the immunity for new therapeutic modalities.
In summary, although we failed to develop a new strategy for anti-cancer therapy using DC-mΦ hybrids, our fusion method formed the technical basis for generation of artificial new immune cells that have two totally different immunological functions. This strategy will provide a new avenue for cell-based immunotherapies. In addition, pharmacological manipulation of GJIC will provide another direction of DC research to control the immunity. Less
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