One of the possible ways to augment dendritic cell (DC) efficacy in presentation of tumor antigens to effector T cells is pulsing them with tumor-cell lysates and incubation with certain immunostimulators. We present the results of an immunotherapeutic approach in a murine B78-H1 model using as a vaccine JAWSII DCs in combination with IL-12. Prior to the in vivo experiments, phenotypic characterization of JAWSII cells was performed and optimal conditions for stimulation of these cells were established. As no production of IL-12 by JAWSII cells was found, injections of this cytokine were introduced to vaccination protocols. Three vaccination schedules have been tested: i) prophylactic, ii) therapeutic-intratumoral, and iii) therapeutic-systemic. In all the protocols, vaccination with pulsed + stimulated JAWSII cells in combination with IL-12 was superior to the treatment with either agent alone and led to eradication of the tumor in several cases. The results of the study may be helpful in planning optimal DC-based therapeutic protocols in cancer patients.