Antibody targeting of phosphatidylserine for the detection and immunotherapy of cancer
Authors Belzile O, Huang X, Gong J, Carlson J, Schroit AJ, Brekken RA, Freimark BD
Received 6 September 2017
Accepted for publication 27 October 2017
Published 23 January 2018 Volume 2018:7 Pages 1—14
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Michael Shurin
Olivier Belzile,1 Xianming Huang,2,3 Jian Gong,2,3 Jay Carlson,2,3 Alan J Schroit,1 Rolf A Brekken,1 Bruce D Freimark2,3
1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Preclinical Research, 3Department of Antibody Discovery, Peregrine Pharmaceuticals, Inc., Tustin, CA, USA
Abstract: Phosphatidylserine (PS) is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses. PS-mediated immunosuppression in the tumor microenvironment is further exacerbated by chemotherapy and radiation treatments that result in increased levels of PS on dying cells and necrotic tissue. Antibodies targeting PS localize to tumors and block PS-mediated immunosuppression. Targeting exposed PS in the tumor microenvironment may be a novel approach to enhance immune responses to cancer.
Keywords: immunosuppression, tumor microenvironment, immunotherapy, imaging, phosphatidylserine, bavituximab
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