Tumour antigen-loaded mouse dendritic cells maturing in the presence of inflammatory cytokines are potent activators of immune response in vitro but not in vivo

Abstract

The use of dendritic cells (DCs) loaded with tumour antigen is one of the most promising approaches to induce tumour-specific immune response. However, methods of the vaccine preparation have not yet been standardized. The purpose of the study was to analyse the anti-tumour efficacy of tumour antigen-loaded mouse bone marrow-derived dendritic cells (BM-DC/TAg) at different maturation stages. BM-DCs were loaded with MC38 colon carcinoma cell lysate (TAg) alone, to become partially differentiated, or were additionally stimulated with inflammatory cytokines such as TNF-α, IFN-γ, or IL-12 to reach complete maturity. BM-DCs simultaneously stimulated with TAg and cytokines (especially IL-12 or IFN-γ+IL-12) were in vitro more effective immune response activators than BM-DC/TAg cells. However, the highest anti-tumour effect in vivo was noted when mice were treated just with BM-DC/TAg. In a further study, the ability of IL-12 gene transduced BM-DCs (BM-DC/IL-12) to augment the immune response induced by BM-DC/TAg cells at different stages of maturation was examined. The highest antitumour effect was observed when partially differentiated BM-DC/TAg cells were injected simultaneously with BM-DC/IL-12 cells. The results suggest that partially differentiated BM-DC/TAg cells are more potent in evoking a strong antitumour response in vivo than mature BM-DCs. Moreover, the capacity of BM-DC/TAg cells for further differentiation and their sensitivity to factors secreted in vivo by the host or cells engineered to cytokine production seem to be of great importance.