Vaccination against the extra domain-B of fibronectin as a novel tumor therapy

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Elisabeth J M HuijbersAnna-Karin Olsson

Abstract

Monoclonal antibody-based therapies have made an important contribution to current treatment strategies for cancer and autoimmune disease. However, the cost for these new drugs puts a significant strain on the health-care economy, resulting in limited availability for patients. Therapeutic vaccination, defined as induction of immunity against a disease-related self-molecule, is therefore an attractive alternative. To analyze the potential of such an approach, we have developed a vaccine against the extra domain-B (ED-B) of fibronectin. This 91-aa domain, inserted by alternative splicing, is expressed during vasculogenesis in the embryo, but essentially undetectable under normal conditions in the adult. However, ED-B is highly expressed around angiogenic vasculature, such as in tumorigenesis. Here, we demonstrate that it is possible to break self-tolerance and induce a strong antibody response against ED-B by vaccination. Nineteen of 20 vaccinated mice responded with production of anti-ED-B antibodies and displayed a 70% reduction in tumor size compared to those lacking anti-ED-B antibodies. Analysis of the tumor tissue revealed that immunization against ED-B induced several changes, consistent with an attack by the immune syste...Continue Reading

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Citations

Dec 8, 2015·Advanced Drug Delivery Reviews·Heena Kumra, Dieter P Reinhardt
Feb 24, 2016·Cellular and Molecular Bioengineering·Karin WangDelphine Gourdon
May 9, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Elisabeth J M HuijbersArjan W Griffioen
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Dec 21, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Falk SaupeAnna-Karin Olsson
Apr 15, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Falk SaupeLars Hellman
Dec 23, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zheng Han, Zheng-Rong Lu
Jan 25, 2017·Human Vaccines & Immunotherapeutics·Elisabeth J M Huijbers, Arjan W Griffioen
Apr 20, 2019·Frontiers in Immunology·Elisabeth J M HuijbersArjan W Griffioen
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