Recently, immune therapy that uses dendritic cells (DCs) has been attempted in many facilities. The results, however, has not been satisfactory. Therefore, DC therapy in which systemic administration of several cytokines (IL-2, etc.) is also used has been attempted. However, systemic administration of cytokines has limitations due to their side effects. Therefore, we decided to focus on romurtide (muramyl dipeptide-Lys, NopiaTM) which is a glycopeptide of the Mycobacterium tuberculosis cell wall skeleton that has a potential enhancement anti-tumor effects. It is well known that muramyl dipeptide modulates the functions of monocyte/macrophages, but its effects on DCs are poorly documented. To determine whether romurtide enhances DC maturation. We examined the effects of romurtide on the expression surface molecules, cytokine secretion, and antigen- presenting function of human monocyte-derived immature DCs (iDCs). We found that romurtide markedly up-regulated the expression of CD83 and CD86 but not human leukocyte antigen-DR (HLA-DR), and stimulated the production of tumor necrosis factor-alpha (TNF-α), and IL-12 by human DCs in a dose-dependent manner. In an allogeneic mixed lymphocyte reaction (MLR), romurtide-treated DCs enhanced antigen-presenting function compared with untreated DCs. Similar results were obtained for DCs from cancer-bearing patients. Altogether, our results demonstrate that romurtide triggers the maturation and activation of monocyte-derived iDCs. As this immunomodulator has been approved for use in humans, it could be a useful adjunct to boost the efficacy of DC-based vaccines designed against tumors.
Kobayashi et al. (Wed,) studied this question.
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