Abstract
Since the prognosis of squamous cell carcinoma (SCC) in the head, neck, and esophagus has shown only a little progress in the last decade, the development of novel therapeutic strategies has been much desired to treat patients with advanced SCC. As a candidate, dendritic cell (DC)-based immunotherapy has been tested, but still requires modification to improve clinical outcomes. We here show that non-transmissible Sendai virus (SeV/dF)-activated DCs (DCs/SeV/dF) has strong antitumor effects against an orthotopic model of murine SCC, namely a less immunogenic SCCVII tumor. SeV/dF showed high transfection efficiency at low MOI to murine bone marrow-derived DCs (mBM-DCs). Higher viral doses of SeV/ dF-GFP did not result in a significant cytopathic effect. SeV/dF leads mBM-DCs to upregulate costimulatory molecules such as CD40, CD80, CD86, and MHC class II. We subsequently assessed the effects of SeV/dF-null transfection on endo-/phagocytotic activity of mBM-DCs. Their activity in taking up FITC-dextran was assessed at various time points after stimulation. Unlinke in DC/ LPS, endo-/phagocytic activity of DCs was not impaired by SeV/ dF. Intratumoral injection of DCs/SeV/dF resulted in a marked and representative inhibition of the tumor, even when the tumors were well-vascularized. The antitumor effects of intratumor injection of DCs/SeV/dF were not impaired without ex vivo exposure of DCs to tumor lysate, suggesting the potential uptake of tumor antigen in vivo. Our results provide the first demonstration that non- transmissible SeV/dF could be a promising candidate for DC- activator; DC/SeV/dF-based cancer immunotherapy may therefore warrant further investigation with regard to its enhancement of antitumor effects in a clinical setting.
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