A Novel Immunostimulator, N²-[α-O-Benzyl-N-(acetylmuramyl)-l-alanyl-d- isoglutaminyl]-N⁶-trans-(m-nitrocinnamoyl)-l-lysine, and Its Adjuvancy on the Hepatitis B Surface Antigen

N²-[α-O-Benzyl-N-(acetylmuramyl)-l-alanyl-d-isoglutaminyl]-N⁶-trans-(m-nitrocinnamoyl)-l-lysine (muramyl dipeptide C, or MDP-C) has been synthesized as a novel, nonspecific immunomodulator. The present study shows that MDP-C induces strong cytolytic activity by macrophages on P388 leukemia cells and cytotoxic activity by cytotoxic T lymphocytes (CTLs) on P815 mastocytoma cells. Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone morrow derived dendritic cells (BMDCs) and production of interferon-γ by CTLs. Additionally, MDP-C increases the expression levels of several surface molecules, including CD11c, MHC class I, and intercellular adhesion molecule-1 in BMDCs. Moreover, MDP-C remarkably enhances the immune system's responsiveness to hepatitis B surface antigen (HBsAg) in hepatitis B virus transgenic mice for both antibody production and specific HBsAg T-cell responses ex vivo. Our results indicate that MDP-C is an apyrogenic, nonallergenic, and low-toxicity immunostimulator with great potential for diagnostic, immunotherapeutic, and prophylactic applications in diseases such as hepatitis B and cancers.