Vaccination of Dendritic Cells Loaded with Interleukin-12-Secreting Cancer Cells Augments In vivo Antitumor Immunity: Characteristics of Syngeneic and Allogeneic Antigen-Presenting Cell Cancer Hybrid Cells

Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
Clinical Cancer Research (Impact Factor: 8.72). 02/2005; 11(1):58-66.
Source: PubMed


Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.

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    • "We speculate that the same effect could not be observed from cells harvested from macrophage-immunized mice due to the intrinsic properties of these APCs in our experimental model. In fact, the low effectiveness of macrophages when compared with DCs in an APC-based immunization model has already been reported (19). Another explanation is based on nonspecific T-cell activation due to bystander effects provided by APCs stimulated via cytokine networks. "
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    • "Thanks to these features, immunostimulatory DC have drawn attention as a useful component for cancer vaccines [5] [6]. DC fused with tumor cells (TCs), more than DC variably loaded with antigenic peptides or apoptotic cells, effectively elicited anti-tumor immunity, both in animal models and in cancer patients [7] [8] [9] [10] [11]. DC–TC hybrids should provide costimulatory proteins and cytokines, in addition to a complete array of tumor antigens presented in the context of class I and II MHC molecules. "
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    • "There is a currently great interest in the assay of polyfunctional T cells, secreting multiple cytokines (e.g., secreting IFN-γ and TNF-α rather than either alone), or expressing multiple surface markers. As the release of Th1 cytokines such as IFN-γ and TNF-α is important to determine long-lasting antitumor immunity, a shift to Th1 response by cancer vaccines is essential for therapeutic potential in murine models [36, 37, 67, 77, 137, 138]. Therefore, it is important to test whether cancer vaccines can induce a Th1 response in the tumor-specific T cells, and what impact might this have on the clinical responses. "
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