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2-26-16/Dr.Raymond.Birge article: “Phosphatidylserine is a Global Immunosuppressive Signal...” - Cell Death & Differentiation, online pub. 2-26-16.

2-26-16: “Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer”
'Cell Death & Differentiation Jrnl' online pub. 2-26-16 (rec.10-31-15; acc.1-7-16)
Raymond Birge 1; S Boeltz 2; S Kumar 1; J Carlson 3; J Wanderley 4; D Calianese 1; M Barcinski5; Rolf Brekken 6,7; Xianming Huang 6,7; Jeff Hutchins 3; Bruce Freimark 3; C Empig 3; J Mercer 8; A J Schroit 9; G Schett 2; Martin Herrmann 2
1. Dept of Microbiology, Biochemistry & Molecular Genetics, CC, Rutgers NJ Medical School, Newark, NJ
2. Dept of Internal Medicine, Rheumatology & Immunology, Friedrich-Alexander-Univ., Erlangen, Germany
3. Peregrine Pharma., Tustin, CA
4. Universidade Federal do Rio de Janeiro, Brazil
5. Lab de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
6. Div. of Surgical Oncology, Hamon Ctr for Therapeutic Oncology Res., UTSW-MC/Dallas
7. Dept of Pharmacology, UTSW-MC/Dallas
8. Medical Research Council Lab for Molecular Cell Biology, Univ. College London
9. Simmons Cancer Center & Dept of Immunology, UTSW-MC/Dallas
ABSTRACT
Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer & infectious disease therapeutics.
FULL ARTICLE: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd201611a.html


= = = = = = = = = =UPCOMING:
June2-4: ICDS 2016: Translational Implications in Cell Death", Cork Ireland http://tinyurl.com/h2gvyld
...Dr. Rolf Brekken (USA, UTSE, PPHM SAB): ”Blockade of PS & Immune Activation in Cancer” (Chair: Dr. Raymond Birge/Rutgers – see http://tinyurl.com/j3whbx3 )

Jun19-22: “ICDS'16 - From Molecules To Diseases”, Istanbul Turkey http://tinyurl.com/h4zjvo4
….Rutgers' Dr. Raymond Birge ( http://birgelab.org ) ”Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer” - see http://tinyurl.com/j3whbx3

= = = = = = = = = = = = =PREV:
June2015: DR RAYMOND BIRGE & Dr. Xianming Huang (Dr.Rolf.Brekken-Lab) at Gordon Res. Conference in Maine on 6-15-15 – speaking next to each other in “Consequences of Lipid Alterations” Session. Peregrine was the only corp. contributor to this conference, specified as, “In Memory of Dr. Philip E. Thorpe.”...

June 14-19, 2015: “Apoptotic Cell Recognition & Clearance”, Gordon Research Conference, Biddeford, ME
Chair: David S. Ucker, Vice Chairs: Peter Henson & Kirsten Lauber
http://www.grc.org/programs.aspx?id=13127
”Moreover, apoptotic cells are potently immunosuppressive, and their clearance occurs in the absence of inflammation. Recognition & inflammatory modulation represent key elements of an innate immunity that discriminates live from effete cells.”
**The only Corp. Sponsor: PEREGRINE PHARM, “Generous financial support from Peregrine Pharmaceuticals is in memory of Dr. Philip E. Thorpe.”
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SESSION: “Consequences of Lipid Alterations for Apoptotic Cell Clearance
Discussion Leader: Christopher Gregory (Univ. of Edinburgh, UK)
7:30pm: Ian Dransfield (Univ. of Edinburgh, UK), “Protein S Binding to Apoptotic Cells...”
8:10pm: Dr. Raymond Birge (Rutgers NJMS), “Apoptotic Cell Recognition Receptors, Tyro3/Axl/Mer...”
8:50pm: Dr. Xianming Huang** (UTSW-MC/Dallas, Brekken Lab), “PS-Targeting Antibodies Overcome Tumor Immunosuppression and Synergize with Immune Checkpoint Blockade"
**Dr. Xianming Huang: formerly in Dr. Philip Thorpe's Lab (RIP, Dr. Thorpe, 1951-2013 http://tinyurl.com/l9gqmt5 ), now in Dr. Rolf Brekken's (PPHM SAB) Lab.
http://www.utsouthwestern.edu/labs/brekken/

= = = = = = = = = = = = = =DR. BIRGE:
...Dr. Raymond Birge has authored ~85 scientific publications in molecular & cancer biology. http://www.ncbi.nlm.nih.gov/pubmed/?term=birge+rb
“The Birge laboratory conducts basic science focused on the eradication of cancer.”
http://birgelab.org => http://birgelab.org/biography.html

====================DR. RAY BIRGE (RUTGERS) & PEREGRINE:
June19-22 2016: “15th Intl. Congress of Histochemistry & Cytochemistry - from Molecules to Diseases”, Istanbul Turkey
“The main goal of ICHC 2016 is to bring the worldwide histochemists together and provide an environment for close cooperation, exchange of information, and collaborations.”
http://www.ichc2016.com
INVITED SPEAKER – Session: “Cellular Aging & Cell Death”
Dr. Raymond Birge (Rutgers Univ. http://birgelab.org ), “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”

Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
...Join Peregrine for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
...Brochure handout (not sure if exactly it): http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets/
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SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly, Duke Univ.** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
The other 2 Duke co-author scientists:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”

Oct29 2015: “John-Hopkins Molecular Microbiology & Immunology Seminar”, Baltimore http://tinyurl.com/oks5uo6
...12-1:00pm: "Phosphatidylserine is a Global Immune Checkpoint In Cancer"
Raymond Birge, PhD, Vice Chair, Professor, Dept of Molecular, Biochemistry & Molecular Genetics, Rutgers Univ., Newark, NJ


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DR. BIRGE, CLEARLY IN STEP WITH DR. THORPE, DR. BREKKEN, AND PEREGRINE PHARMACEUTICALS...

5-1-12/NYAS: Dr. Philip Thorpe (UTSW, RIP/1951-2013) on Bavi MOA: http://tinyurl.com/9792gl5
“As a 2nd mechanism, bavituximab can overcome the immunosuppressive processes observed with cells that externalize PS. In tumors the expression of PS on cell surfaces keeps macrophages in their M2 state, an activation state that suppresses inflammation and supports angiogenesis. It also prevents myeloid-derived suppressor cells (MDSCs) from differentiating into macrophages and dendritic cells (DCs). In addition, PS inhibits the maturation of DCs, which prevents the presentation of antigens to T cells. Bavituximab repolarizes macrophages to their M1 state, which allows them to kill cells that express PS, including the tumor vascular endothelium. It also leads to differentiation of the MDSCs and prompts DCs to mature and to present tumor antigens to T cells.”

5-28-14/NYAS: Dr. Rolf Brekken (UTSW) http://tinyurl.com/lq9stnk
“Phosphatidylserine (PS) is a potent immunosuppressive lipid typically segregated to the inner leaflet of the plasma membrane. PS is externalized on tumor vasculature, tumor-derived exosomes, and tumor cells in the tumor microenvironment and externalization is enhanced by therapy. Externalized PS interacts with immune cells where it actively promotes expansion of myeloid derived suppressor cells (MDSCs) and M2-like tumor associated macrophages (TAMs), which drive immunosuppression and tumor progression. In preclinical studies, treatment of tumor-bearing mice with murine-versions of bavituximab significantly depleted M2-likeTAMs & MDSCs and increased the presence of M1-like TAMs and mature dendritic cells. In addition, PS blockade shifted the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. Furthermore, in the immune-competent tumor models combination of standard of care therapy with PS blockade induced potent durable tumor-specific T-cell immunity and significantly improved tumor free long-term survival. These data suggest that externalized PS defines a global immune checkpoint in tumors and support that antibody-mediated PS blockade can reverse PS-mediated immune checkpoint suppression, revitalize innate and the adaptive immunity, and promote therapeutically effective anti-tumor immunity.”

1-16-16/PR: About Bavituximab: A Targeted Investigational Immunotherapy”
“Bavituximab is an investigational immunotherapy designed to assist the body's immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine's PS targeted inhibitor, bavituximab, is thought to reverse the immunosuppressive environment that many tumors establish in order to proliferate and spread, while also fighting cancer by activating immune cells that target and fight cancer.”
“Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab blocks PS and, in turn, is believed to remove this immunosuppressive signal and send an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=949704

3-1-2014/Youtube: “Cancer Research” - Dr. Raymond Birge Laboratory, Rutgers http://birgelab.org
http://www.youtube.com/watch?v=HdacTc_I7Js
Dr. Ray Birge/2:54: "The immune system is very complex and if it can recognize tumors as being foreign to the body, then it can reactivate & eliminate these tumors to treat as a chronic disease, or in some cases eliminate the tumors. One of the projects that our lab is interested in is how to reactivate the immune system toward particular cancers, and we believe that the type of cell death that cancer cells undergo will determine whether or not they'll be an immune reaction against the cancer. If cells die, through a process called apoptosis, in a certain way, they can reactivate / activate the immune system and give a durable, anti-tumor response. The problem that we're trying to understand is how the tumor cells evade the immune system and therefore block these immune-suppressing signals to reactivate the immune system against cancer..."