TY - JOUR
T1 - Vaccination against the extra domain-B of fibronectin as a novel tumor therapy
AU - Huijbers, Elisabeth J M
AU - Ringvall, Maria
AU - Femel, Julia
AU - Kalamajski, Sebastian
AU - Lukinius, Agneta
AU - Abrink, Magnus
AU - Hellman, Lars
AU - Olsson, Anna-Karin
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Animals
KW - Antibodies, Monoclonal/immunology
KW - Antibody Formation/immunology
KW - Cancer Vaccines/immunology
KW - Cell Line, Tumor
KW - Fibronectins/immunology
KW - Mice
KW - Mice, Inbred C57BL
KW - Models, Immunological
KW - Models, Molecular
KW - Neoplasms/pathology
KW - Protein Structure, Tertiary
U2 - 10.1096/fj.10-163022
DO - 10.1096/fj.10-163022
M3 - Article
C2 - 20634349
VL - 24
SP - 4535
EP - 4544
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 11
ER -