title: Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer.
abstract: Therapeutic vaccination targeting self-molecules is an attractive alternative to monoclonal antibody-based therapies for cancer and various inflammatory diseases. However, development of cancer vaccines targeting self-molecules has proven difficult. One complicating factor is that tumor cells have developed strategies to escape recognition by the immune system. Antigens specifically expressed by the tumor vasculature can therefore provide alternative targets. The alternatively spliced extra domain-A and B (ED-A and ED-B) of fibronectin are expressed during vasculogenesis in the embryo, but essentially undetectable under normal conditions in the adult. However, these domains are re-expressed during tumor angiogenesis and matrix remodeling, which renders them highly interesting for targeted cancer therapies. Using the MMTV-PyMT transgenic model of metastatic mammary carcinoma, we show that tumor burden can be significantly decreased by immunization against ED-A in a therapeutic setting. Furthermore, we found that in mice carrying anti-ED-A antibodies the number of metastases was reduced. ED-A immunization increased infiltration of macrophages and compromised tumor blood vessel function. These findings implicate an attack of the tumor vasculature by the immune system, through a polyclonal antibody response. We conclude that tumor vascular antigens are promising candidates for development of therapeutic vaccines targeting growth of primary tumors as well as disseminated disease.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala.
authors.forename: Julia
authors.initials: J
authors.lastname: Femel
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala.
authors.forename: Elisabeth J M
authors.initials: EJ
authors.lastname: Huijbers
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala.
authors.forename: Falk
authors.initials: F
authors.lastname: Saupe
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cedervall
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Roswall
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala.
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala.
authors.forename: Helena
authors.initials: H
authors.lastname: Olofsson
authors.affiliation: Department of Laboratory Medicine, Lund University, Medicon Village AB, Lund.
authors.forename: Kristian
authors.initials: K
authors.lastname: Pietras
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala.
authors.forename: Anna
authors.initials: A
authors.lastname: Dimberg
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hellman
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Olsson
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy
chemical_list: D019496:Cancer Vaccines; D005353:Fibronectins