Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Natascha Stergiou
  • Nikola Gaidzik
  • Anne-Sophie Heimes
  • Sarah Dietzen
  • Pol Besenius
  • Joerg Jaekel
  • Walburgis Brenner
  • Marcus Schmidt
  • Horst Kunz
  • Edgar Schmitt
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000454826000011&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1158/2326-6066.CIR-18-0256
eISSN
2326-6074
Externe Identifier
  • Clarivate Analytics Document Solution ID: HG2VV
  • PubMed Identifier: 30413430
ISSN
2326-6066
Ausgabe der Veröffentlichung
1
Zeitschrift
CANCER IMMUNOLOGY RESEARCH
Paginierung
113 - 122
Datum der Veröffentlichung
2019
Status
Published
Titel
Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid
Sub types
  • Article
Ausgabe der Zeitschrift
7

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>Abstract</jats:title> <jats:p>Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfactory therapeutic effects, indicating an urgent need to improve humoral immunity against this tumor entity. Herein, we demonstrate that preventive vaccination against tumor-associated human MUC1 results in a specific humoral immune response, a slowdown of tumor progression and an increase in survival of breast tumor–bearing mice. For preventive vaccination, we used a synthetic vaccine containing a tumor-associated glycopeptide structure of human MUC1 coupled to Tetanus Toxoid. The glycopeptide consists of a 22mer huMUC1 peptide with two immune dominant regions (PDTR and GSTA), glycosylated with the sialylated carbohydrate STN on serine-17. PyMT (polyomavirus middle T-antigen) and human MUC1 double-transgenic mice expressing human tumor-associated MUC1 on breast tumor tissue served as a preclinical breast cancer model.</jats:p>
Autoren
  • Natascha Stergiou
  • Nikola Gaidzik
  • Anne-Sophie Heimes
  • Sarah Dietzen
  • Pol Besenius
  • Jörg Jäkel
  • Walburgis Brenner
  • Marcus Schmidt
  • Horst Kunz
  • Edgar Schmitt
DOI
10.1158/2326-6066.cir-18-0256
eISSN
2326-6074
ISSN
2326-6066
Ausgabe der Veröffentlichung
1
Zeitschrift
Cancer Immunology Research
Sprache
en
Online publication date
2019
Paginierung
113 - 122
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
American Association for Cancer Research (AACR)
Herausgeber URL
http://dx.doi.org/10.1158/2326-6066.cir-18-0256
Datum der Datenerfassung
2022
Titel
Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid
Ausgabe der Zeitschrift
7

Datenquelle: Crossref

Abstract
Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfactory therapeutic effects, indicating an urgent need to improve humoral immunity against this tumor entity. Herein, we demonstrate that preventive vaccination against tumor-associated human MUC1 results in a specific humoral immune response, a slowdown of tumor progression and an increase in survival of breast tumor-bearing mice. For preventive vaccination, we used a synthetic vaccine containing a tumor-associated glycopeptide structure of human MUC1 coupled to Tetanus Toxoid. The glycopeptide consists of a 22mer huMUC1 peptide with two immune dominant regions (PDTR and GSTA), glycosylated with the sialylated carbohydrate ST<sub>N</sub> on serine-17. PyMT (polyomavirus middle T-antigen) and human MUC1 double-transgenic mice expressing human tumor-associated MUC1 on breast tumor tissue served as a preclinical breast cancer model.
Addresses
  • Institute of Immunology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Autoren
  • Natascha Stergiou
  • Nikola Gaidzik
  • Anne-Sophie Heimes
  • Sarah Dietzen
  • Pol Besenius
  • Jörg Jäkel
  • Walburgis Brenner
  • Marcus Schmidt
  • Horst Kunz
  • Edgar Schmitt
DOI
10.1158/2326-6066.cir-18-0256
eISSN
2326-6074
Externe Identifier
  • PubMed Identifier: 30413430
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: 1066 project B13
Open access
false
ISSN
2326-6066
Ausgabe der Veröffentlichung
1
Zeitschrift
Cancer immunology research
Schlüsselwörter
  • Cell Line, Tumor
  • Animals
  • Mice, Transgenic
  • Humans
  • Mammary Neoplasms, Experimental
  • Glycopeptides
  • Immunoglobulin G
  • Vaccines, Synthetic
  • Cancer Vaccines
  • Tetanus Toxoid
  • Antibodies, Monoclonal
  • Middle Aged
  • Female
  • Mucin-1
  • Triple Negative Breast Neoplasms
Sprache
eng
Medium
Print-Electronic
Online publication date
2018
Paginierung
113 - 122
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2018
Titel
Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
7

Datenquelle: Europe PubMed Central

Abstract
Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfactory therapeutic effects, indicating an urgent need to improve humoral immunity against this tumor entity. Herein, we demonstrate that preventive vaccination against tumor-associated human MUC1 results in a specific humoral immune response, a slowdown of tumor progression and an increase in survival of breast tumor-bearing mice. For preventive vaccination, we used a synthetic vaccine containing a tumor-associated glycopeptide structure of human MUC1 coupled to Tetanus Toxoid. The glycopeptide consists of a 22mer huMUC1 peptide with two immune dominant regions (PDTR and GSTA), glycosylated with the sialylated carbohydrate STN on serine-17. PyMT (polyomavirus middle T-antigen) and human MUC1 double-transgenic mice expressing human tumor-associated MUC1 on breast tumor tissue served as a preclinical breast cancer model.
Date of acceptance
2018
Autoren
  • Natascha Stergiou
  • Nikola Gaidzik
  • Anne-Sophie Heimes
  • Sarah Dietzen
  • Pol Besenius
  • Jörg Jäkel
  • Walburgis Brenner
  • Marcus Schmidt
  • Horst Kunz
  • Edgar Schmitt
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30413430
DOI
10.1158/2326-6066.CIR-18-0256
eISSN
2326-6074
Ausgabe der Veröffentlichung
1
Zeitschrift
Cancer Immunol Res
Schlüsselwörter
  • Animals
  • Antibodies, Monoclonal
  • Cancer Vaccines
  • Cell Line, Tumor
  • Female
  • Glycopeptides
  • Humans
  • Immunoglobulin G
  • Mammary Neoplasms, Experimental
  • Mice, Transgenic
  • Middle Aged
  • Mucin-1
  • Tetanus Toxoid
  • Triple Negative Breast Neoplasms
  • Vaccines, Synthetic
Sprache
eng
Country
United States
Paginierung
113 - 122
PII
2326-6066.CIR-18-0256
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Titel
Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
7

Datenquelle: PubMed

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