In vivo biotinylation of the vasculature in B-cell lymphoma identifies BST-2 as a target for antibody-based therapy.
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.
Schliemann
Christoph
C
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
Roesli
Christoph
C
Kamada
Haruhiko
H
Borgia
Beatrice
B
Fugmann
Tim
T
Klapper
Wolfram
W
Neri
Dario
D
D000465:Algorithms; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D019921:Biotinylation / Q000502:physiology; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D007116:Immunization, Passive / Q000379:methods; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009368:Neoplasm Transplantation / Q000276:immunology / Q000473:pathology; D040081:Protein Array Analysis; D014185:Transplantation, Isogeneic; D000074010:Bone Marrow Stromal Antigen 2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; C513868:BST2 protein, mouse; D000074010:Bone Marrow Stromal Antigen 2