Dendritic cell (DC)—tumor fusion hybrid vaccine that facilitates antigen presentation represents a new, powerful strategy in cancer therapy. We investigated the antitumor immunity derived from vaccination of fusion hybrids between wild-type J558 or engineered J558-IL-4 myeloma cells secreting cytokine interleukin-4 (IL-4) and DCs. The design and methods for generation of mature bone marrow-derived DCs, preparation of DC/J558-IL-4 hybrid, and in vivo animal studies of DC/myeloma hybrid vaccine are described. Our data show that the fusion efficiency was approx 20% by using polyethylene glycol. Our data also show that immunization of C57BL/6 mice with engineered DC/J558-IL-4 hybrids elicited stronger J558 tumor-specific cytotoxic T-lymphocyte responses in vitro and induced more efficient protective immunity against J558 tumor challenge in vivo than DC/J558 hybrid vaccines.