| Murine tumor models have contributed much to our understanding of immune rejection processes and afford an opportunity for monitoring the in vivo therapeutic effects of cancer vaccines, adoptively transferred T cells, and bone marrow transplantation (BMT). Dendritic cells (DC), as potent antigen presenting cells, allow whole tumor lysates to be used as a source of tumor-associated antigen(s) for presentation to the immune system. This research project involves studies of murine DC-based cancer vaccines in the setting of syngeneic BMT. Tumor lysate-pulsed dendritic cells (TP-DC) could prime a specific and long-lasting antitumor immune response after BMT, which mediated the rejection of a lethal challenge of a weakly-immunogenic mammary carcinoma. In the therapeutic setting, repetitive immunizations of TP-DC could inhibit the growth of pre-existing tumor metastases as well. Because interleukin-7 (IL-7) has been shown by others to be capable of expediting hematolymphoid reconstitution and mediating antitumor immunity, this cytokine was combined with TP-DC immunizations in an attempt to enhance therapeutic efficacy. Although the systemic administration of IL-7 alone could stimulate hematolymphoid reconstitution, it had no effect on mediating antitumor immunity in the BMT setting. In addition, when used as an adjunct to TP-DC immunizations, IL-7 appeared to negate the antitumor immune response afforded by the vaccine. The antitumor therapeutic efficacy of TP-DC could, however, be further improved by an adoptive immunotherapy strategy. The bone marrow and lymph nodes of TP-DC immunized hosts contain tumor-reactive immune cells, which, when adoptively transferred to the BMT recipients, could mediate the regression of pre-existing metastatic tumors. The antitumor effect manifested by these tumor-reactive immune cells appeared to be tumor-specific and dependent on T cells. The secretion of Th1-type cytokines, including IFN-γ and GM-CSF, by these tumor-reactive effector cells was detected. Collectively, these findings provide evidence for the antitumor efficacy of DC-based vaccines in the setting of syngeneic BMT and may have important implications for human clinical trials involving autologous bone marrow transplantations in cancer patients. |
