Vaccination against the extra domain-B of fibronectin as a novel tumor therapy.
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
Elisabeth J M
EJ
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Ringvall
Maria
M
Femel
Julia
J
Kalamajski
Sebastian
S
Lukinius
Agneta
A
Abrink
Magnus
M
Hellman
Lars
L
Olsson
Anna-Karin
AK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005353:Fibronectins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D008958:Models, Molecular; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D005353:Fibronectins