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1-23-18: New Dovepress article by UTSW+PPHM on PS-Targeting immunotherapy for cancer, concluding that, “targeting exposed PS in the tumor microenvironment may be a novel approach to enhance immune responses to cancer”. Gives a history of PS-Targeting (Bavituximab), both pre-clinical studies and human trials to date. For SUNRISE, for Results (Table 3), it says, “Manuscript in preparation”.

1-23-18/DovePress: “Antibody Targeting of Phosphatidylserine for the Detection & Immunotherapy of Cancer”
Rec: 9-6-17, Acc: 10-27-17, Pub: 1-23-18 (14 pgs.)
Olivier Belzile 1 Xianming Huang 2,3 Jian Gong 2,3 Jay Carlson 2,3 Alan J Schroit 1 Rolf A Brekken 1 Bruce Freimark 2,3
1 Hamon Center for Therapeutic Oncology Res.s, UTSW/MC/Dallas
2 Dept of Preclinical Res., Peregrine Pharm.
3 Dept of Antibody Discovery, Peregrine Pharm.
https://www.dovepress.com/antibody-targeting-of-phosphatidylserine-for-the-detection-and-immunot-peer-reviewed-article-ITT
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 & radiation treatments that result in increased levels of PS on dying cells & 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.
LINK TO FULL PDF (14pgs): https://www.dovepress.com/getfile.php?fileID=40225
CONCLUSION:
PS is well-recognized as a cell surface marker of apoptotic cells which provides signals to specific receptors for noninflammatory efferocytosis by phagocytes. The same signals are usurped in the tumor microenvironment by the exposure of PS on tumor blood vessel endothelium and tumor cells, contributing to immunosuppression and tolerance of tumor growth. Specific receptors that bind PS, including TIMs and TAMs, on immune cells and tumors, trigger these immunosuppressive pathways. The uptake of PS-targeting antibodies by tumors is readily demonstrated in preclinical models and initial clinical studies. Multiple preclinical studies serve as proof of concept that the antibody-mediated blockade of PS in tumors can reactivate innate & adaptive immune responses in the tumor microenvironment. A combination of PS-targeting antibodies with approved immune activating therapies such as chemotherapy, radiation, and immune checkpoint inhibitors (including antibodies targeting CTLA-4, PD-1, and PD-L1) and with novel therapies such as oncolytic viruses has the potential to treat a variety of different tumor types. These data support clinical trial evaluation of the PS-targeting antibody, bavituximab, in multiple oncology indications.
ACKNOWLEDGMENTS
We acknowledge the Dept’s of Clinical & Regulatory Affairs and Process Sciences at Peregrine Pharmaceuticals, for current insight on the clinical development of bavituximab and for providing antibodies for preclinical studies. We also thank Steve King for helpful technical discussions and support of preclinical studies and Dave Primm for editorial assistance.