Self-adjuvanting synthetic antitumor vaccines from MUC1 glycopeptides conjugated to T-cell epitopes from tetanus toxoid.

2013

The T-helper epitope peptide P30 (green in the scheme) from tetanus toxoid was used as the immunostimulant in MUC1 glycopeptide antitumor vaccines and apparently also acts as a built-in adjuvant. P30-conjugated glycopeptide vaccines containing three glycans in the immunodominant motifs PDTRP and GSTAP induced much stronger immune responses and complement dependent cytotoxicity mediated killing of tumor cells when applied in plain PBS solution without complete Freund's adjuvant.

Towards a fully synthetic MUC1-based anticancer vaccine: efficient conjugation of glycopeptides with mono-, di-, and tetravalent lipopeptides using c…

2011

Abstract The membrane-bound tumor-associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor-associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune-stimulating toll-like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid-phase synthesis of the MUC1 glycopeptides. The Pam(3) Cys lipopeptide, also synthesized on solid-phase, was C-terminally coupled to oligovalent lysine…

Multivalente synthetische Glycopeptid-Lipopeptid-Antitumorvakzine: Auswirkung des Cluster-Effekts auf das Abtöten von Tumorzellen

2014

Multivalente synthetische Vakzine wurden durch Festphasensynthese von tumorassoziierten MUC1-Glycopeptidantigenen und deren Kupplung an ein Pam3Cys-Lipopeptid durch Klick-Reaktion gewonnen. Diese Vakzine losen in Mausen Immunreaktionen aus, ohne dass externe Adjuvantien angewendet werden. Die vier MUC1-Sialyl-TN-Antigene enthaltende Vakzine zeigte einen signifikanten Cluster-Effekt. Sie induzierte in Mausen vorwiegend IgG2a-Antikorper, die an MCF-7-Brusttumorzellen binden und diese Tumorzellen durch Aktivierung des Complement-abhangigen Cytotoxizitatskomplexes (CDC) abtoten.

Synthetic MUC1 Antitumor Vaccine Candidates with Varied Glycosylation Pattern Bearing R/S-configured Pam3 CysSerLys4.

2016

The Toll-like receptor 2 ligand Pam3 CysSer is of particular interest for the construction synthetic vaccines because of its ability to stimulate of the innate immune system. Such vaccines usually comprise Pam3 CysSer with the natural R-configuration at the glycerol 2-position. Pam3 CysSer peptide vaccines with natural configuration have been shown to be more efficient than the corresponding R/S diastereomers. In order to clarify whether the effect of the configuration of Pam3 Cys on the immune response also applies to glycopeptide vaccines, MUC1 glycopeptide-lipopeptide vaccines bearing either R- or R/S-configured Pam3 CysSerLys4 were compared for their immunological effects. In order to f…

Variation of the glycosylation pattern in MUC1 glycopeptide BSA vaccines and its influence on the immune response.

2012

MUC1-Glycopeptidkonjugate mit T-Zellepitopen von Tetanus-Toxoid als vollsynthetische Antitumor-Vakzine mit Eigenverstärkungseffekt

2013

Fully synthetic self-adjuvanting thioether-conjugated glycopeptide-lipopeptide antitumor vaccines for the induction of complement-dependent cytotoxic…

2012

Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3)Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam(3)CSK(4) lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund's adjuvant or in aqueous PBS buffer. The three-compon…

Fully synthetic vaccines consisting of tumor-associated MUC1 glycopeptides and a lipopeptide ligand of the Toll-like receptor 2.

2010

Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the cluster effect on the killing of tumor cells.

2014

Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.

Variation des Glycosylierungsmusters von Vakzinen aus MUC1- Glycopeptiden und Rinderserumalbumin und der Einfluss auf die Immunreaktion

2012

Vollsynthetische Vakzinen aus tumorassoziierten MUC1-Glycopeptiden und einem Lipopeptid-Liganden des Toll-like Rezeptors 2

2010

Synthesis of Tn/T Antigen MUC1 Glycopeptide BSA Conjugates and Their Evaluation as Vaccines

2011

The tumor-associated mucin MUC1 over-expressed in most epithelial tumor tissues is considered a promising target for immunotherapy. The extracellular part of MUC1 contains a domain of numerous tandem repeats of the amino acid sequence HGVTSAPDTRPAPGSTAPPA, including five potential O-glycosylation sites. In this study, T9 and S15 have been chosen as the positions of glycosylation. The glycopeptides N-terminally equipped with a triethylene glycol spacer were synthesized by microwave-assisted Fmoc solid-phase peptide synthesis. After detachment from the resin and deprotection, the MUC1 glycopeptides were conjugated to bovine serum albumin (BSA). To evaluate the immunological properties, balb/c…