Muramyl Dipeptide modulates differentiation, maturity of dendritic cells and anti-tumor effect of DC-mediated T cell in acute leukemia children

Abstract

Background:Targeted therapy is a potentially useful approach for antileukemic therapy, in particular eliminating minimal residual disease(MRD) to prevent tumor relapse. This study was aimed to find out an effective, nontoxic dendritic cell (DC) maturating agent for the immunotherapy of acute leukemia. Results: MDP-matured DCs(M-DCs) expressed higher level of phenotypic markers and secreted higher cytokine level, while lower than TNF-α-matured DCs (T-DCs) and co-administration of MDP and TNF-α-matured DCs (MT-DCs). MT-DCs promoted significantly allogeneic T-cells reaction. As a result, allogeneic T-cell proliferated significantly and secreted higher amount of IFN-γ. HL60-derived antigens were presented more effectively by MT-DCs to cytotoxic T lymphocytes (CTLs) to induce more beneficial anti-tumor effects in a dose-dependent manner. Methods: Purified mononuclear cells (MNCs) from bone marrow of acute leukemia children were differentiated by granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant human interleukin-4 (rhIL-4) and further matured by either Muramyl Dipeptide（MDP), tumor necrosis factor-alpha (TNF-α) or co-administration of MDP and TNF-α. Conclusions: These results demonstrate MDP can be used as a candidate clinical agent for antigen specific cancer immunotherapy.