Replies to post #152773 on Avid Bioservices Inc (CDMO)

[cjgaddy]

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

[biopharm]

ALSO, this most compelling quote from a new NATURE article (pub. 12-19-13), ”Bacteriology: A Caring Culture”, a special article on Dr. William Coley's** legacy and modern efforts to defeat cancer

http://www.nature.com/nature/journal/v504/n7480_supp/full/504S4a.html?WT.ec_id=NATURE-20131219

nice post and also a nice look back from Dr. Brekkens "Revitalizing Tumor Immunity" from Science & Technology magazine.

Back to William Coley though, we have some mention from CRI Day#28 of family member Coley in regard to the patient profile of Donald F. (Sarcoma) ..

....Luckily for Donald, his doctor at the time knew about some unconventional research being done at Memorial Hospital in New York under the direction of Bradley Coley, M.D.

Bradley Coley is the son of William Bradley Coley, M.D., the 19th century New York surgeon widely hailed as the “Father of Cancer Immunotherapy.” Bradley’s sister, Helen Coley Nauts, was the founder of the Cancer Research Institute (CRI). Both Bradley and Helen believed strongly in the value of William Coley’s approach to treating cancer.
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http://www.theanswertocancer.org/online-community-for-cancer-immunotherapy/stories-from-patients-and-caregivers/donald-foley-patient-story

William Coley Bio:

http://en.wikipedia.org/wiki/William_Coley

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Jan 2001

William Coleys daughter = Helen Coley Nauts

In 1953, she established the Cancer Research Institute, which now has an annual budget of $14 million and provides support for scientists around the world. She eventually succeeded in returning her father's work to the attention of oncologists.

''She was inflamed,'' said Dr. Lloyd J. Old, an immunotherapy expert at Sloan-Kettering and a longtime friend. ''She was absolutely inflamed by a grand idea.''

Dr. Coley is now often described as the founder of modern immunotherapy, a major cancer treatment. Although Coley's toxins are rarely used, his discoveries of the late 19th century are credited with helping researchers develop more modern therapies. And Mrs. Nauts has received many awards for her work.
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About two years later, Mrs. Nauts went to the medical director of Dr. Coley's hospital and said she thought that her father's work deserved reappraisal. Her best course of action, she was told, was to put together 100 or so case histories; she eventually produced 1,000, along the way educating herself about cancer. She was so precise that cancer researchers today still examine the monographs she published for clues about the disease, Dr. Old said.

In an interview with Science, Mrs. Nauts described a meeting with a Mount Sinai Hospital bacteriologist, Dr. Gregory Shwartzman, with whom her father had corresponded.

''I had read Shwartzman's book on the reaction of tumors to bacteria, and had prepared 13 pages of questions based on it,'' Mrs. Nauts recalled. ''During the interview, I took 80 pages of notes. Shwartzman couldn't believe anyone could be that thorough. But because I had no medical education, I had to be that way.''

In the years that followed, Mrs. Nauts wrote thousands of letters to doctors and patients who had used her husband's methods, seeking specifics about their cases. Her efforts were not always welcomed by the medical establishment.

''At times the response to her could be described as vitriolic,'' said Dr. Alan M. Houghton, chairman of immunotherapy at Sloan-Kettering. But Mrs. Nauts was unyielding, and as the field of immunotherapy grew, researchers recognized the value of Dr. Coley's once-ignored work.

http://www.nytimes.com/2001/01/09/nyregion/helen-c-nauts-93-champion-of-her-father-s-cancer-work.html

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Seems to be a common there, the medical establishment or Big Pharma as we know it..... resisting any movement of advancement into the science of cancer immunotherapy, because it simply removes control and revenue from Big Pharma. Big Pharma nervous with PS Targeting ? Hell yeah