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

• Published in: The FASEB journal 2010-11, Vol.24 (11), p.4535-4544
• Main Authors: Huijbers, Elisabeth J.M, Ringvall, Maria, Femel, Julia, Kalamajski, Sebastian, Lukinius, Agneta, Åbrink, Magnus, Hellman, Lars, Olsson, Anna-Karin
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; Antibodies, Monoclonal - immunology; Antibody Formation - immunology; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Cell Line, Tumor; extracellular matrix; Fibronectins - immunology; immunization; MEDICIN; MEDICINE; Mice; Mice, Inbred C57BL; Models, Immunological; Models, Molecular; Neoplasms - pathology; Neoplasms - therapy; neovascularization; Protein Structure, Tertiary; therapeutic
• ISSN: 0892-6638; 1530-6860; 1530-6860
• DOI: 10.1096/fj.10-163022

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 system. These data show that tumor vascular antigens are highly interesting candidates for development of therapeutic vaccines targeting solid tumors.--Huijbers, E. J. M., Ringvall, M., Femel, J., Kalamajski, S., Lukinius, A., Åbrink, M., Hellman, L., Olsson, A.-K. Vaccination against the extra domain-B of fibronectin as a novel tumor therapy.