Cell Fusion and Dendritic Cell-Based Vaccines

Abstract

Fusions of dendritic cells (DC) and tumor cells are increasingly used in tumor immunotherapy. The strategy for DC-tumor fusion vaccine is based on the fact that DC are the most potent antigen-presenting cells in the body, whereas tumor cells express abundant tumor antigens. The fusion of these two cell types creates a heterokaryon with both DC-derived costimulatory molecules, efficient antigen-processing and -presentation machinery, and tumor-derived antigens. In animal and human studies, fusion-cell (FC) vaccines have been shown to possess the elements essential for processing and presenting tumor antigens to host immune cells, for inducing effective immune response, and for breaking T-cell tolerance to tumor-associated antigens. Moreover, FC vaccines provide protection against challenge with tumor cells and mediate regression of established tumors. Despite these unique features of DC-tumor fusion cells and the observation of tumor eradication in animal studies, only limited, yet encouraging, success has been seen in clinical trials. This chapter describes the methods used for preparation of DC-tumor fusion cells, summarizes the effect of FC in stimulating T cell responses, analyzes factors influencing the success or failure of FC-mediated immunotherapy and discusses recent advances in concept and techniques of DC-tumor fusions.