Mtppe

Figure 3 Chemical structures of various MDP derivatives applied to clinical trials.

adjuvanticity but shows no substantial activity regarding nonspecific resistance to infection. Clinical trials using B30-MDP as an adjuvant effect in an influenza virus vaccine demonstrate that it is able to induce both humoral and cellular immunity. MTP-PE has been shown to be highly effective in generating tumoricidal properties of macrophages. Lipo-some-encapsulated MTP-PE (L-MTP-PE) has been designed for in vivo targeting to macrophages and decreasing side-effects, and is in clinical trials for cancer. A series of derivatives replacing the D-isoglut-aminyl residue with D-glutamine alkyl esters of various sizes was shown to be active but much less pyro-genic than MDP. The representative derivative of this series is murabutide, a compound which does not elicit any febrile response in animal experiments.

Clinical trials of murabutide as a vaccine adjuvant and as a potentiator of nonspecific resistance to infection are currently in progress.

Allison and coworkers found that a MDP analog, N-acetylmuramyl-L-threonyl-D-isoglutamine (MDP (Thr)) retained potent adjuvant activity but was less pyrogenic in rabbits and rats. MDP(Thr) has been applied as an immunoadjuvant with the vehicle 'Syn-tex Adjuvant Formulation, SAF', which consists of pleuronic 1.121, squalane, Tween 80 and PBS.

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