1Health Research Divison, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7N 4H4, Canada 2Departments of Oncology, Biology and Geography, University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada
Abstract. Aim: Dendritic cell — tumor cell fusion hybrid vaccines which facilitate antigen presentation represent a new powerful strategy in cancer immunotherapy. The clinical frequency of objective responses to the conventional fusion hybrid vaccines is still quite low, indicating that the current conventional protocol of simply fusing dendritic cells (DCs) and tumor cells needs further improvement to enhance its antitumor efficiency. Methods: In the present study, we generated a novel fusion hybrid DC/J558CD40L by fusing DCs and an engineered J558CD40L myeloma cells expressing CD40 ligand (CD40L) molecule using polyethylene glycol (PEG). The fusion efficiency was approximately 20%. We investigated the antitumor immunity derived from vaccination of the fusion hybrid DC/J558CD40L. Results: Our results showed that vaccination of mice with DC/J558CD40L hybrids induced more efficient cytotoxic T lymphocyte (CTL) responses and protective immunity against J558 tumor cells, than that of the conventional fusion hybrid DC/J558 from the fusion of DCs and J558 tumor cells. The antitumor immunity derived from vaccination of DC/J558CD40L was mainly mediated by CD4+ and CD8+cT cells, but not natural killer (NK) cells. Conclusion: Therefore, this novel fusion hybrid vaccine which combines gene-modified tumor and DC vaccines may be an attractive strategy for cancer immunotherapy.
