An atlas of bloodstream-accessible bone marrow proteins for site-directed therapy of acute myeloid leukemia.

Autor: Angenendt L; Department of Medicine A, University Hospital Münster, Münster, Germany., Reuter S; Department of Medicine D, University Hospital Münster, Münster, Germany., Kentrup D; Department of Medicine D, University Hospital Münster, Münster, Germany., Benk AS; HI-STEM gGmbH and German Cancer Research Center, Heidelberg, Germany., Neumann F; Fluorescence Microscopy Facility Münster, Institute of Medical Physics and Biophysics, Center for Nanotechnology, University of Münster, Münster, Germany., Hüve J; Fluorescence Microscopy Facility Münster, Institute of Medical Physics and Biophysics, Center for Nanotechnology, University of Münster, Münster, Germany., Martens AC; Department of Hematology, University Hospital Utrecht, Utrecht, The Netherlands., Schwöppe C; Department of Medicine A, University Hospital Münster, Münster, Germany., Kessler T; Department of Medicine A, University Hospital Münster, Münster, Germany., Schmidt LH; Department of Medicine A, University Hospital Münster, Münster, Germany., Sauer T; Department of Medicine A, University Hospital Münster, Münster, Germany.; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA., Brand C; Department of Medicine A, University Hospital Münster, Münster, Germany., Mikesch JH; Department of Medicine A, University Hospital Münster, Münster, Germany., Lenz G; Department of Medicine A, University Hospital Münster, Münster, Germany.; Translational Oncology, University Hospital Münster, Münster, Germany.; Cluster of Excellence EXC 1003, Cells in Motion, Münster, Germany., Mesters RM; Department of Medicine A, University Hospital Münster, Münster, Germany., Müller-Tidow C; Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany., Hartmann W; Gerhard Domagk-Institute for Pathology, University Hospital Münster, Münster, Germany., Wardelmann E; Gerhard Domagk-Institute for Pathology, University Hospital Münster, Münster, Germany., Neri D; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland., Berdel WE; Department of Medicine A, University Hospital Münster, Münster, Germany., Roesli C; HI-STEM gGmbH and German Cancer Research Center, Heidelberg, Germany., Schliemann C; Department of Medicine A, University Hospital Münster, Münster, Germany.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2018 Feb; Vol. 32 (2), pp. 510-519. Date of Electronic Publication: 2017 Jun 30.
DOI: 10.1038/leu.2017.208
Abstrakt: The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tumor tissue but is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream. In total, >1400 proteins were identified. Overall, 181 proteins were >100-fold overexpressed in AML as compared with normal BM. Eleven of the most differentially expressed proteins were further validated by immunohistochemistry and confocal microscopic analyses, including novel antigens highly expressed in AML cells (for example, adaptor-related protein complex 3 β2) and in the leukemia-modified extracellular matrix (ECM) (for example, collagen-VI-α-1). The presented atlas of targetable AML-associated BM proteins provides a valuable basis for the development of monoclonal antibodies that could be used as carriers for a site-specific pharmacodelivery of cytotoxic drugs, cytokines or radionuclides to the BM in AML.
Databáze: MEDLINE
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