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The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment.

Dendritic cells (DCs) are potent professional antigen-presenting cells and play a critical role in the induction of primary immune responses. DC-based vaccination represents a potentially powerful strategy for cancer immunotherapy. Thus, the use of cancer vaccines to eliminate residual tumor cells is a promising area of investigation. The immunotherapy of tumor antigen-loaded DCs has now been demonstrated in cancer patients and some clinical responses without any significant toxicity. Fusions of DCs and tumor cells represent an alternative but promising approach to overcome the inability of tumor antigens to induce a sustainable T-cell response. This review deals with recent progress in the immunotherapy of cancer with fusions of DCs and tumor cells.

Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination.

A promising area of investigation is the use of cancer vaccines to eliminate residual tumor cells. Dendritic cells (DCs) are potent professional antigen-presenting cells able to induce primary immune responses. DCs capture and process antigens into peptides and present them to T cells and B cells through MHC class I and II molecules. An alternative approach to the induction of antitumor immunity is the use of fusions of DCs and tumor cells. In this approach, a broad spectrum of tumor-associated antigens, including those known and unidentified, are processed endogenously and presented by MHC class I and II pathways in the context of costimulatory signals. In animal studies, vaccination with DC/tumor fusion cells results in the elimination of established lung metastasis. Preclinical human studies have demonstrated that DC/tumor fusion cells induce antigen-specific polyclonal cytotoxic T-lymphocyte responses against autologous tumor in vitro. In clinical studies, vaccination of cancer patients with autologous DC/tumor fusion cells is associated with immunological and clinical responses in a subset of patients. Future studies should be investigated to improve the immunogenicity of DC/tumor fusion cell preparations. This review provides a general overview of the DC/tumor fusion cell-based vaccine and summarizes some of the recent advances in this field.

Dendritic/tumor fusion cell (FC) vaccine is an effective approach for various types of cancer but has not yet been standardized. Antitumor activity can be modulated by different mechanisms such as dendritic cell (DC) maturation state. This study addressed optimal strategies for FC preparations to enhance Ag-specific CTL activity. We have created three types of FC preparations by alternating fusion cell partners: 1) immature DCs fused with autologous colorectal carcinoma cells (Imm-FCs); 2) Imm-FCs followed by stimulation with penicillin-inactivated Streptococcus pyogenes (OK-432) (Imm-FCs/OK); and 3) OK-432-stimulated DCs directly fused to autologous colorectal carcinoma cells (OK-FCs). Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs. Short-term culture of fusion cell preparations promoted the fusion efficiency. Interestingly, OK-FCs were more efficient in stimulating CD4(+) and CD8(+) T cells capable of high levels of IFN-gamma production and cytolysis of autologous tumor or semiallogeneic targets. Moreover, OK-FCs are more effective inducer of CTL activation compared with Imm-FCs/OK on a per fusion cell basis. The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency. Furthermore, the cryopreserved OK-FCs retained stimulatory capacity for inducing antitumor immunity. These results suggest that OK-432 promotes fusion efficiency and induction of Ag-specific CTL by fusion cells. We conclude that DCs fused after stimulation by OK-432 may have the potential applicability to the field of antitumor immunotherapy and may provide a platform for adoptive immunotherapy in the clinical setting.