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Dr. R.Brekken’s 3-25-14/NYAS Talk on PS-Targeting/Immune Checkpoint Blockade (45-Slides)…

Mar25 2014 12-4pm: “New York Academy of Sciences (NYAS) Symposium”, 7WTC/NYC
Symposium Name: “Lung Cancer: Advances in Current Treatment Modalities & Patient Classification”
NYAS: http://www.nyas.org/WhatWeDo/Default.aspx
“Recent treatment advances may improve lung cancer patient survival rates, as understanding genetic heterogeneity can improve trial patient selection. Hear updates on common mutations, intraoperative chemotherapy, and insights from clinical trials.”
http://www.nyas.org/Events/Default.aspx
Link to this NYAS Lung Cancer Symposium: http://tinyurl.com/kr8k72w (NYAS.org)
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PRESENTED BY: The Biochemical Pharmacology Discussion Group at the New York Academy of Sciences
ORGANIZERS
• Magdalena Alonso-Galicia, PhD - Forest Research Institute
• Shashidhar S. Jatiani, PhD - Forest Research Institute
• Huiping Jiang, PhD - Boehringer-Ingelheim Pharmaceuticals
• George Zavoico, PhD - HC Wainwright (formerly, MLV)
• Jennifer Henry, PhD - The New York Academy of Sciences
SPEAKERS
• Jessica S. Donington, MD - NYU Langone Medical Center
• Roy S. Herbst, MD, PhD - Yale School of Medicine
• Balazs Halmos, MD - Columbia Univ. Medical Center
• Suresh S. Ramalingam, MD - Emory Univ.
• Rolf Brekken, PhD – UTSW-MC/Dallas (also: SAB/PPHM)
SYMPOSIA DESC: Lung cancer is one of the most common and deadliest cancers worldwide. The majority of patients present with advanced disease and despite decades of work, overall survival rates are still very low. Recent advances in treatment modalities have increased the risk/benefit ratio for these patients and this may translate into increased survival rates. A better understanding of the genetic heterogeneity of lung cancer has led to a new patient classification scheme that may help inform on patient selection for future trials. The topics to be discussed in this symposium include: lung cancer classification, common mutations and insights for patient selection, the use of intraoperative chemotherapy and minimally invasive surgery to treat thoracic cancers, and a discussion on insights from clinical trials using targeted and combination chemotherapy for small cell & non-small cell lung cancers.
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3-25-14 3:20-4:00pm: “Antibody-mediated Inhibition of Phosphatidylserine: A Novel Strategy for Immune Checkpoint Blockade”, Dr. Rolf Brekken, PhD, UTSW-MC/Dallas
DR. BREKKEN’s ABSTRACT:
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. Bavituximab is a PS-targeting antibody that is being evaluated clinically in cancer patients. In preclinical studies, treatment of tumor-bearing mice with 2aG4 or mch1N11 (murine-versions of bavituximab) significantly depleted M2-likeTAMs and 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.
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Dr. Brekken’s 3-25-14 NYAS 45-pg. Slideshow (40min. talk):
Dr. Rolf Brekken, 3-25-14, NYAS Lung Cancer Symposium (UTSW-MC/Dallas, SAB/PPHM)
“Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade”
Dr. Brekken’s UTSW Lab website: http://www.utsouthwestern.edu/labs/brekken


























































































*END BREKKEN 3-25-2014/NYAS*
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PS-TARGETING SCIENCE: "Evolution has favored pathogenesis that resembles apoptosis."
Dr. Judah Folkman: ”This [Thorpe’s VTA research] is very promising and very elegant work... The whole goal is really 2-part, reducing the harsh side effects of cancer treatment, and reducing the chance that some cancer cells will evade treatment. That would be a big step in the next decade, and anti-vascular therapy will play a major role." (’97 & ’02 http://tinyurl.com/k5qe96g & http://tinyurl.com/n6vh9hp )
Peregrine's Bavituximab & Cotara Technologies: http://www.peregrineinc.com/technology/overview.html
Peregrine's Bavi & Cotara Clinical Trials website: http://PeregrineTrials.com
Bavi MOA: 4-min Video on Bavi’s Immunotherapeutic Moa added to PeregineInc.com on 1-13-2014: http://tinyurl.com/mbd3kta
BAVI MOA: 3-25-14 Dr. Rolf Brekken’s 40min talk at NYAS Lung Cancer Symposium http://tinyurl.com/lq9stnk
. . .Dr.Brekken’s talk: “Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade”
. . .The 5 speakers: Jessica Donington, Roy Herbst, Balazs Halmos, Suresh Ramalingam, Rolf Brekken
BAVI MOA: 12-2013 Bavi’s Immunotherapeutic MOA overviewed by UTSW’s Brekken/Huang in Pan European Networks Jrnl. http://tinyurl.com/lnb46pq
BAVI MOA 11-9-13: Annual SITC (WashDC) – 2 posters about Bavi’s Immunostimulatory MOA http://tinyurl.com/mjaweu5
...“We are actively working towards initiating a clinical trial in the coming months to further investigate the potential synergistic effects of bavituximab and an approved [anti-CTLA-4] immunotherapy in patients with Melanoma."
10-28-13 IASLC/Sydney: “Immune Checkpoints in the Tumor Environment: Novel Targets & the Clinical Promise of Combined Immunotherapies” http://tinyurl.com/mjaweu5
…Symposium speakers: Scott J. Antonia/MD-PhD(H.Lee Moffitt CC), Dmitry I. Gabrilovich/MD-PhD(Wistar Inst), Rolf A. Brekken/PhD(UTSW), David E. Gerber/MD(UTSW)
BAVI MOA: 8-19-13 Data Supporting Bavituximab’s Immunotherapy MOA Published in “Cancer Immunology Research” (AACR) - http://tinyurl.com/mhjftka (PDF)
…“PS-Targeting Antibody Induces M1 Macrophage Polarization & Promotes Myeloid-Derived Suppressor Cell Differentiation” (Thorpe etal)
BAVI MOA: 8-13-13 PPHM/VP Dr. Jeff Hutchins’ Presentation on the Downstream Immunostimulatory Effects/Moa of PS-targeting antibodies (like Bavi) at CHI’s “Immunotherapies Congress”/Boston http://tinyurl.com/m6h2tvt
BAVI MOA: 10-12-12 NMB article on how Bavi "Induces Innate & Specific Anti-tumor Responses" http://tinyurl.com/cw9odb8
BAVI MOA: 5-1-12 Dr. Phil Thorpe's 46min talk at NYAS PS-Targeting Symposium http://tinyurl.com/9792gl5
. . .Symposium title: "Phosphatidylserine (PS) Asymmetry - Therapeutic Apps. in Cancer & Infectious Disease Symposium"
. . .Replays of 5 speakers: Alan Schroit, Chris Reutlingsperger, David Ucker, Ari Helenius, Philip Thorpe
BAVI MOA: 5-26-11 Dr.Thorpe's keynoter at Recombinant-Mabs/Barcelona http://tinyurl.com/3klpodc & http://tinyurl.com/3m33h33
BAVI MOA: See http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html