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Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer.

Femel, Julia; Huijbers, Elisabeth J M; Saupe, Falk; Cedervall, Jessica; Zhang, Lei; Roswall, Pernilla; Larsson, Erik; Olofsson, Helena; Pietras, Kristian LU and Dimberg, Anna, et al. (2014) In Oncotarget 5(23). p.12418-12427
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,... (More)
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. (Less)
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Oncotarget
volume
5
issue
23
pages
12418 - 12427
publisher
Impact Journals, LLC
external identifiers
  • pmid:25360764
  • wos:000348037700049
  • scopus:84919969583
ISSN
1949-2553
language
English
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yes
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b6a61c12-c1f0-4173-845d-5c3a5f0a78e2 (old id 4820447)
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http://www.ncbi.nlm.nih.gov/pubmed/25360764?dopt=Abstract
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2014-12-01 18:24:53
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2017-06-11 04:20:00
@article{b6a61c12-c1f0-4173-845d-5c3a5f0a78e2,
  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.},
  author       = {Femel, Julia and Huijbers, Elisabeth J M and Saupe, Falk and Cedervall, Jessica and Zhang, Lei and Roswall, Pernilla and Larsson, Erik and Olofsson, Helena and Pietras, Kristian and Dimberg, Anna and Hellman, Lars and Olsson, Anna-Karin},
  issn         = {1949-2553},
  language     = {eng},
  number       = {23},
  pages        = {12418--12427},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer.},
  volume       = {5},
  year         = {2014},
}