Lipopeptide adjuvants in combination treatment.
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.
Bessler
Wolfgang G
WG
Institut für Molekulare Medizin und Zellforschung, Universitätsklinikum Freiburg, Stefan-Meier-Str. 8, D-79104 Fribourg, Germany. wolfgang.bessler@mol-med.uni-freiburg.de
Mittenbühler
K
K
Esche
U v d
Uv
Huber
M
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D005260:Female; D005903:Gliadin / Q000276:immunology; D008074:Lipoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D008074:Lipoproteins; D013745:Tetanus Toxoid; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D009569:Nitric Oxide; D005903:Gliadin