0000000000006569

AUTHOR

Ulrika Westerlind

Synthetische Antitumor-Vakzine aus MUC1-Glycopeptiden mit zwei immundominanten Domänen - Induktion einer starken Immunreaktion gegen Brusttumorgewebe

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

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A Synthetic Vaccine Consisting of a Tumor-Associated Sialyl-TN-MUC1 Tandem-Repeat Glycopeptide and Tetanus Toxoid: Induction of a Strong and Highly Selective Immune Response

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Ein synthetischer Impfstoff aus einem tumorassoziierten Sialyl-TN-MUC1-Tandem-Repeat-Glycopeptid und Tetanustoxoid zur Induktion einer starken, hochselektiven Immunantwort

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Antibody Induction Directed against the Tumor-Associated MUC4 Glycoprotein

Mucin glycoproteins are important diagnostic and therapeutic targets for cancer treatment. Although several strategies have been developed to explore anti-tumor vaccines based on MUC1 glycopeptides, only few studies have focused on vaccines directed against the tumor-associated MUC4 glycoprotein. MUC4 is an important tumor marker overexpressed in lung cancer and uniquely expressed in pancreatic ductual adenocarcinoma. The aberrant glycosylation of MUC4 in tumor cells results in an exposure of its peptide backbone and the formation of tumor-associated glycopeptide antigens. Due to the low immunogenicity of these endogenous structures, their conjugation with immune stimulating peptide or prot…

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Tumor-Associated MUC1 Tandem-Repeat Glycopeptide Microarrays to Evaluate Serum- and Monoclonal-Antibody Specificity

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Inside Cover: Antibody Induction Directed against the Tumor-Associated MUC4 Glycoprotein (ChemBioChem 6/2015)

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Glycopeptide-functionalized gold nanoparticles for antibody induction against the tumor associated mucin-1 glycoprotein

We report the preparation of gold nanoparticle (AuNP)-based vaccine candidates against the tumor-associated form of the mucin-1 (MUC1) glycoprotein. Chimeric peptides, consisting of a glycopeptide sequence derived from MUC1 and the T-cell epitope P30 sequence were immobilized on PEGylated AuNPs and the ability to induce selective antibodies in vivo was investigated. After immunization, mice showed significant MHC-II mediated immune responses and their antisera recognized human MCF-7 breast cancer cells. Nanoparticles designed according to this report may become key players in the development of anticancer vaccines.

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Inside Back Cover: Microarray Analysis of Antibodies Induced with Synthetic Antitumor Vaccines: Specificity against Diverse Mucin Core Structures (Chem. Eur. J. 16/2017)

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Synthetische Vakzine aus tumorassoziierten MUC1-Glycopeptidantigenen und einem T-Zellepitop für die Induzierung einer hochspezifischen humoralen Immunantwort

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Advances in N ‐ and O ‐Glycopeptide Synthesis – A Tool to Study Glycosylation and Develop New Therapeutics

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Preparation of Biomolecule Microstructures and Microarrays by Thiol-ene Photoimmobilization

A mild, fast and flexible method for photoimmobilization of biomolecules based on the light-initiated thiol-ene reaction has been developed. After investigation and optimization of various surface materials, surface chemistries and reaction parameters, microstructures and microarrays of biotin, oligonucleotides, peptides, and MUC1 tandem repeat glycopeptides were prepared with this photoimmobilization method. Furthermore, MUC1 tandem repeat glycopeptide microarrays were successfully used to probe antibodies in mouse serum obtained from vaccinated mice. Dimensions of biomolecule microstructures were shown to be freely controllable through photolithographic techniques, and features down to 5 …

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Titelbild: Tumor-Associated MUC1 Tandem-Repeat Glycopeptide Microarrays to Evaluate Serum- and Monoclonal-Antibody Specificity (Angew. Chem. 44/2009)

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The development of synthetic antitumour vaccines from mucin glycopeptide antigens.

Based on important cell-biological and biochemical results concerning the structural difference between membrane glycoproteins of normal epithelial cells and epithelial tumour cells, tumour-associated glycopeptide antigens have been chemically synthesised and structurally confirmed. Glycopeptide structures of the tandem repeat sequence of mucin MUC1 of epithelial tumour cells constitute the most promising tumour-associated antigens. In order to generate a sufficient immunogenicity of these endogenous structures, usually tolerated by the immune system, these synthetic glycopeptide antigens were conjugated to immune stimulating components: in fully synthetic two-component vaccines either with…

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Synthetische Antitumorvakzine aus Tetanus-Toxoid-Konjugaten von MUC1-Glycopeptiden mit Thomsen-Friedenreich-Antigen und dessen fluorsubstituiertem Analogon

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Antitumor Vaccines Based on Synthetic Mucin Glycopeptides

The interest in tumor-associated glycoconjugate antigens was particularly initiated by Springer, who published in 1984 that glycoproteins on the outer cell-membrane of epithelial tumor cells have an altered glycosylation consisting of the Thomsen-Friedenreich (T-) antigen and its precursor the TN-antigen structure (Springer 1984). He and his coworkers also had found that monoclonal antibodies induced with glycoproteins from tumor cell membranes showed cross-reactivity to desialylated glycophorin A. It was concluded from these observations that the T-and TN-glycoproteins on the epithelial tumor cells must be structurally related to asialoglycophorin A (Springer et al. 1983) (Fig. 11.1a). Gly…

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ChemInform Abstract: The Development of Synthetic Antitumor Vaccines from Mucin Glycopeptide Antigens

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Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and a T-cell epitope for the induction of a highly specific humoral immune response.

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Microarray analysis of antibodies induced with synthetic antitumor vaccines : specificity against diverse mucin core structures

Glycoprotein research is pivotal for vaccine development and biomarker discovery. Many successful methodologies for reliably increasing the antigenicity toward tumor-associated glycopeptide structures have been reported. Deeper insights into the quality and specificity of the raised polyclonal, humoral reactions are often not addressed, despite the fact that an immunological memory, which produces antibodies with cross-reactivity to epitopes exposed on healthy cells, may cause autoimmune diseases. In the current work, three MUC1 antitumor vaccine candidates conjugated with different immune stimulants are evaluated immunologically. For assessment of the influence of the immune stimulant on a…

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Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues.

A shot in the arm for cancer treatment: two MUC1 tetanus toxoid vaccines were synthesized and induced a strong immune response in mice. The antibodies elicited by the vaccines show a high selectivity for the tumor cells in mammary carcinoma tissues and also distinguish between tumor tissues at different stages.

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Cover Picture: Tumor-Associated MUC1 Tandem-Repeat Glycopeptide Microarrays to Evaluate Serum- and Monoclonal-Antibody Specificity (Angew. Chem. Int. Ed. 44/2009)

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