Lipopeptide adjuvants in combination treatment

Abstract

Synthetic lipopeptides derived from the N-terminus of bacterial lipoprotein constitute potent immunoadjuvants for parenteral and mucosal immunization. When combined with tetanus toxoid (TT) or gliadin as antigens, the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (P(3)CSK(4)) markedly enhanced the specific antibody levels. Lipopeptides also act as macrophage/monocyte activators: P(3)CSK(4) induced nitric oxide release from bone marrow-derived macrophages (BMDM) of LPS responder and nonresponder mice. The antitumoral effect of the lipopeptide was demonstrated by a strong cytostatic activity of the lipopeptide-treated macrophages against the murine B-cell lymphoma cell line Abelson 8-1. The chemically well-defined lipopeptides can be synthesized with high purity and reproducibility and constitute ideal agents to be combined with antigens/vaccines or antitumor treatment.