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In vivo biotinylation of the vasculature in B-cell lymphoma identifies BST-2 as a target for antibody-based therapy.

Abstract
The discovery of accessible markers of lymphoma may facilitate the development of antibody-based therapeutic strategies. Here, we describe the results of a chemical proteomic study, based on the in vivo biotinylation of vascular proteins in lymphoma-bearing mice followed by mass spectrometric and bioinformatic analysis, to discover proteins expressed at the tissue-blood border of disseminated B-cell lymphoma. From a list of 58 proteins, which were more than 10-fold up-regulated in nodal and extranodal lymphoma lesions compared with their levels in the corresponding normal host organs, we validated BST-2 as a novel vascular marker of B-cell lymphoma, using immunochemical techniques and in vivo biodistribution studies. Furthermore, targeting BST-2 with 2 independent monoclonal antibodies delayed lymphoma growth in a syngeneic mouse model of the disease. The results of this study delineate a strategy for the treatment of systemic B-cell lymphoma in humans and suggest that anti-BST-2 antibodies may facilitate pharmacodelivery approaches that target the tumor-stroma interface.
AuthorsChristoph Schliemann, Christoph Roesli, Haruhiko Kamada, Beatrice Borgia, Tim Fugmann, Wolfram Klapper, Dario Neri
JournalBlood (Blood) Vol. 115 Issue 3 Pg. 736-44 (Jan 21 2010) ISSN: 1528-0020 [Electronic] United States
PMID19903902 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Neoplasm
  • BST2 protein, mouse
  • Membrane Glycoproteins
Topics
  • Algorithms
  • Animals
  • Antibodies, Monoclonal (therapeutic use)
  • Antigens, CD (immunology, metabolism, physiology)
  • Antigens, Neoplasm (immunology, metabolism)
  • Biotinylation (physiology)
  • Blood Vessels (immunology, metabolism)
  • Cell Line, Tumor
  • Female
  • Immunization, Passive (methods)
  • Lymphoma, B-Cell (metabolism, pathology, therapy)
  • Membrane Glycoproteins (antagonists & inhibitors, immunology, metabolism, physiology)
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Neoplasm Transplantation (immunology, pathology)
  • Protein Array Analysis
  • Transplantation, Isogeneic

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