Development of immunoadjuvants for immunotherapy of cancer.

Previously, we have reported that cell-wall skeleton (CWS) fraction was the major adjuvant-active principle of mycobacterial cells which were used in Freund's complete adjuvant (FCA). We have described the biochemical and immunological properties of CWS of mycobacteria and related bacteria, especially the CWS of Mycobacterium bovis BCG strain (BCG-CWS) in detail. The effectiveness of BCG-CWS for the cancer immunotherapy in patients was shown in several clinical trials. On the action mechanism of BCG-CWS on host immune cells, we have suggested that dendritic cells and macrophages express two sorts of receptors, Toll-like receptors, TLR-2 and TLR-4, and a putative binding receptor for BCG-CWS, whose signaling pathways lead to a sufficient antigen-presenting state in the activation of the innate immune system. We have also reported the usefulness of synthetic immunoadjuvants such as muramyldipeptide (MDP) derivatives, trehalose-dimycolates (TDM) and DNA fraction for the application for the cancer and infectious diseases in experimental systems and cancer patients.