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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

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

Author

  • Julia Femel
  • Elisabeth J M Huijbers
  • Falk Saupe
  • Jessica Cedervall
  • Lei Zhang
  • Pernilla Roswall
  • Erik Larsson
  • Helena Olofsson
  • Kristian Pietras
  • Anna Dimberg
  • Lars Hellman
  • Anna-Karin Olsson
Show all

Summary, in English

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.

Department/s

  • Division of Translational Cancer Research
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2014

Language

English

Pages

12418-12427

Publication/Series

Oncotarget

Volume

5

Issue

23

Document type

Journal article

Publisher

Impact Journals

Topic

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1949-2553