Synthetic Antitumor Vaccines from Tetanus Toxoid Conjugates of MUC1 Glycopeptides with the Thomsen-Friedenreich Antigen and a Fluorine-Substituted Analogue

被引：121

作者：

Hoffmann-Roder, Anja ^{[1
]}

Kaiser, Anton ^{[1
]}

Wagner, Sarah ^{[1
]}

Gaidzik, Nikola ^{[1
]}

Kowalczyk, Danuta ^{[1
]}

Westerlind, Ulrika ^{[2
]}

Gerlitzki, Bastian ^{[3
]}

Schmitt, Edgar ^{[3
]}

Kunz, Horst ^{[1
]}

机构：

[1] Johannes Gutenberg Univ Mainz, Inst Organ Chem, D-55128 Mainz, Germany

[2] Gesell Forderung Analyt Wissensch eV, ISAS, Inst Analyt Sci, D-44227 Dortmund, Germany

[3] Johannes Gutenberg Univ Mainz, Univ Med Mainz, Inst Immunol, D-55101 Mainz, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2010年 / 49卷 / 45期

关键词：

antitumor vaccines; glycopeptides; MUC1; tetanus toxoid; Thomsen-Friedenreich antigen; T-CELL EPITOPE; COUPLING REAGENT; INDUCTION; BINDING;

D O I：

10.1002/anie.201003810

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A "shot in the arm" for cancer therapy: Coupling of synthetic glycopeptide tandem-repeat sequences of the epithelial mucin MUC1 with the Thomsen-Friedenreich (T) antigen (A) or a difluoro analogue (B) to tetanus toxoid (TTox) affords synthetic vaccines, which induce very strong immune responses in mice overriding the natural tolerance of the immune system. The induced antibodies are selectively directed against the tumor-associated MUC1 structures and strongly bind to breast cancer cells of the MCF-7 cell line. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：8498 / 8503

页数：6

共 29 条

[1] Synthetic tumor-associated glycopeptide antigens from the tandem repeat sequence of the epithelial mucin MUC4 [J].

Brocke, C ;

Kunz, H .

SYNTHESIS-STUTTGART, 2004, (04) :525-542

[2] 1-HYDROXY-7-AZABENZOTRIAZOLE - AN EFFICIENT PEPTIDE COUPLING ADDITIVE [J].

CARPINO, LA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (10) :4397-4398

[3] O-BENZOTRIAZOLYL-N,N,N',N'-TETRAMETHYLURONIUM HEXAFLUOROPHOSPHATE AS COUPLING REAGENT FOR THE SYNTHESIS OF PEPTIDES OF BIOLOGICAL INTEREST [J].

DOURTOGLOU, V ;

GROSS, B ;

LAMBROPOULOU, V ;

ZIOUDROU, C .

SYNTHESIS-STUTTGART, 1984, (07) :572-574

[4] A fully synthetic vaccine consisting of a tumor-associated glycopeptide antigen and a T-Cell epitope for the induction of a highly specific humoral immune response [J].

Dziadek, S ;

Hobel, A ;

Schmitt, E ;

Kunz, H .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (46) :7630-7635

[5] Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and bovine serum albumin [J].

Dziadek, S ;

Kowalczyk, D ;

Kunz, H .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (46) :7624-7630

[6] Synthesis and structural model of an α(2,6)-sialyl-T glycosylated MUC1 eicosapeptide under physiological conditions [J].

Dziadek, Sebastian ;

Griesinger, Christian ;

Kunz, Horst ;

Reinscheid, Uwe M. .

CHEMISTRY-A EUROPEAN JOURNAL, 2006, 12 (19) :4981-4993

[7]

FRECHET JMJ, 1975, TETRAHEDRON LETT, P3055

[8]

GENDLER SJ, 1990, J BIOL CHEM, V265, P15286

[9] MUC1:: the polymorphic appearance of a human mucin [J].

Hanisch, FG ;

Müller, S .

GLYCOBIOLOGY, 2000, 10 (05) :439-449

[10] Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc [J].

Ju, Tongzhong ;

Aryal, Rajindra P. ;

Stowell, Caleb J. ;

Cummings, Richard D. .

JOURNAL OF CELL BIOLOGY, 2008, 182 (03) :531-542

← 1 2 3 →