Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
UNM begins testing of new cancer-fighting drug
The University of New Mexico Comprehensive Cancer Center successfully completed the first in-human testing of a promising new cancer drug called BXQ-350 that is meant to target solid malignant tumors.
Dr. Olivier Rixe has been involved in the development of BXQ-350 from the early stages of its conception and is the director of the clinical trial at UNM.
“You have a lot of steps with the (U.S. Food and Drug Administration),” he said. “It’s almost been 10 years from the initial concept to the first patients treated.”
The drug works by targeting a protein called phosphatidylserine, also known as PS, that is usually present in the inner cell membrane and plays a key role in cell signaling.
Rixe said in contrast to healthy cells, the PS protein is expressed on the outer membrane of cancerous cells......
http://www.dailylobo.com/article/2017/10/new-cancer-drug
Thanks for that link!
Inhibition of Suicidal Erythrocyte Death by Volasertib
https://www.karger.com/Article/FullText/481969
Abstract
Background/Aims: The Polo-like kinase 1 (Plk1) inhibitor volasertib is used in the treatment of malignancy. Volasertib is partially effective by triggering suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal cell death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Stimulators of eryptosis include energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether volasertib impacts on eryptosis. Methods: Human erythrocytes have been exposed to energy depletion (glucose withdrawal for 48 hours), hyperosmotic shock (addition of 550 mM sucrose for 6 hours), oxidative stress (addition of 0.3 mM tert-butylhydroperoxide [tBOOH] for 50 min) or Ca2+ ionophore ionomycin (1 µM for 60 min) in absence and presence of volasertib (0.5-1.5 µg/ml) and flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3 fluorescence, reactive oxygen species from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence and ceramide abundance utilizing antibodies. For comparison, annexin-V-binding and forward scatter were determined following a 48 hours exposure of human leukemic K562 cells in RPMI-1640 medium to volasertib. Results: Treatment with volasertib alone did not significantly modify annexin-V-binding or forward scatter in mature erythrocytes. Energy depletion, hyperosmotic shock, oxidative stress and ionomycin, all markedly and significantly increased the percentage of annexin-V-binding erythrocytes, and decreased the forward scatter. Volasertib significantly blunted the effect of energy depletion and hyperosmotic shock, but not of oxidative stress and ionomycin on annexin-V-binding. Volasertib did not significantly influence the effect of any maneuver on forward scatter. In K562 cells, volasertib enhanced annexin-V-binding and decreased the forward scatter. Conclusions: Volasertib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and hyperosmotic shock, effects contrasting the stimulation of K562 cell apoptosis.
Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment.
Kumar S1, Calianese D1, Birge RB1.
Author information
1New Jersey Medical School, Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University, Newark, NJ, USA.
Abstract
Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell-derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis). To this end, apoptotic cells express specific eat-me signals, such as externalized phosphatidylserine (PS), that are recognized in a specific context by receptors to initiate signaling pathways for engulfment. The importance of carefully regulated recognition and clearance pathways is evident in the spectrum of inflammatory and autoimmune disorders caused by defects in PS receptors and signaling molecules. However, in recent years, several additional cell death pathways have emerged, including immunogenic cell death, necroptosis, pyroptosis, and netosis that interweave different cell death pathways with distinct innate and adaptive responses from classical apoptosis that can shape long-term host immunity. In this review, we discuss the role of different cell death pathways in terms of their immune potential outcomes specifically resulting in specific cell corpse/phagocyte interactions (phagocytic synapses) that impinge on host immunity, with a main emphasis on tolerance and cancer immunotherapy.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
https://www.ncbi.nlm.nih.gov/pubmed/29027226
Necroptotic cell death in anti-cancer therapy.
Krysko O1, Aaes TL2,3,4, Kagan VE5,6, D'Herde K7, Bachert C1, Leybaert L7, Vandenabeele P2,3,4, Krysko DV4,7.
Author information
1Upper Airway Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University, Ghent, Belgium.VIB-UGent Center for Inflammation Research (IRC), VIB, Ghent, Belgium.Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
Abstract
Necroptosis is one the best-characterized forms of regulated necrosis. Necroptosis is mediated by the kinase activities of receptor interacting protein kinase-1 and receptor interacting protein kinase-3, which eventually lead to the activation of mixed lineage kinase domain-like. Necroptosis is characterized by rapid permeabilization of the plasma membrane, which is associated with the release of the cell content and subsequent exposure of damage-associated molecular patterns (DAMPs) and cytokines/chemokines. This release underlies the immunogenic nature of necroptotic cancer cells and their ability to induce efficient anti-tumor immunity. Triggering necroptosis has become especially important in experimental cancer treatments as an alternative to triggering apoptosis because one of the hallmarks of cancer is the blockade or evasion of apoptosis. In this review, we discuss recent advances in necroptosis research and the functional consequences of necroptotic cancer cell death, with focus on its immunogenicity and its role in the activation of anti-tumor immunity. Next, we discuss the molecular mechanisms of phosphatidylserine exposure during necroptosis and its role in the recognition of necroptotic cells. We also highlight the complex role of the necroptotic pathway in tumor promotion and suppression and in metastasis. Future studies will show whether necroptosis is truly a better strategy to overcome apoptosis resistance and provide the insights needed for development of novel treatment strategies for cancer.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
https://www.ncbi.nlm.nih.gov/pubmed/29027225
Dana-Farber Cancer Institute Joins the Parker Institute for Cancer Immunotherapy - PRN
16-Oct-2017 14:00
Dana-Farber Cancer Institute Joins the Parker Institute for Cancer ImmunotherapyCollaborative Relationship Integrates More of the Brightest Minds in Cancer Immunotherapy to Accelerate Research and Save Lives PR Newswire
SAN FRANCISCO and BOSTON, Oct. 16, 2017
SAN FRANCISCO and BOSTON, Oct. 16, 2017 /PRNewswire-USNewswire/ -- The Parker Institute for Cancer Immunotherapy (http://www.parkerici.org/) today announced that researchers at Dana-Farber Cancer Institute (http://www.dana-farber.org/) have joined its network. Dana-Farber is a leader in cancer research and brings a team of experts who will collaborate with Parker Institute investigators to enhance and expand research projects and clinical trials. Dana-Farber's expansive clinical trial capabilities and strong immuno-oncology research approach will complement the current work at the Parker Institute, specifically in checkpoint inhibitor resistance.
Leadership at both institutions have worked together to identify projects that support the Parker Institute's strategic roadmap. Projects include those focused on basic mechanisms underlying checkpoint inhibitor resistance and immune activation and priming. Clinical research could include trials that integrate checkpoint therapies with cancer vaccines. In many cases, these projects will be collaborations with Parker Institute investigators at other institutions.
"Dana-Farber has been involved in the Parker Institute from the beginning, and President and CEO Laurie Glimcher played a critical role in the development of our model and our research strategy," said Jeffrey Bluestone, Ph.D., CEO and president of the Parker Institute. "Dana-Farber is a longstanding innovator in oncology and has a very strong history of collaboration. Its team of outstanding investigators will add immense value to our network and help accelerate the development of cancer immunotherapies with the greatest chance of impact on patients."
The Parker Institute created a flexible model to easily expand its network and recruit world-class talent like the researchers at Dana-Farber. The researchers joining the Parker Institute include:
Nick Haining, BCh, BM, is a physician-scientist at Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT who studies the mechanisms underlying T cell exhaustion and immune evasion by tumors. Dr. Haining's lab uses cellular immunology, functional genomics, epigenetics and single cell profiling to understand why protective T cell memory fails to occur in cancer and chronic viral infection, and how tumors avoid immune attack.
Catherine Wu, M.D., is an internationally recognized physician-scientist with expertise in cancer genomics, immunogenomics and the design and testing of personalized cancer vaccines. A major priority of her studies is the identification of tumor-specific antigens that would allow effective tumor targeting without collateral toxicity. She is an Associate Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School and Institute Member of the Broad Institute of Harvard and MIT.
Philip Kranzusch, Ph.D., is an Assistant Professor in the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and the Department of Microbiology and Immunobiology at Harvard Medical School. His lab uses structural and biochemical approaches to understand how the immune system recognizes cancer and is currently focused on harnessing the cGAS-STING pathway to control immune signaling and antitumor immunity.
F. Stephen Hodi, Jr., M.D., is an internationally recognized leader in developing immune therapy and melanoma therapeutics, particularly known for the clinical development of checkpoint inhibitors. He led the first human trial of ipilimumab, which blocks the CTLA-4 checkpoint. This later led to the phase III registration trial, which was the first study to show a survival advantage for a melanoma drug, leading to FDA approval of ipilimumab. Dr. Hodi has continued as a key investigator in the clinical development of the second family of checkpoint inhibitors, which block PD-1 and PD-L1, and have improved outcomes in many other malignancies, such as lung and kidney cancer. "We are thrilled to be joining the Parker Institute research endeavor. The best way to make a huge impact in the field of oncology is to work collaboratively with leading researchers and institutions. This approach will help us overcome barriers that stand in the way of developing revolutionary therapies," said Laurie H. Glimcher, M.D., president and CEO of Dana-Farber Cancer Institute and a member of the Parker Institute's scientific steering committee. "Dana-Farber is continuing to advance the rapid progress seen in immuno-oncology over the past five to 10 years, and we are honored to be part of the impressive team that the Parker Institute has convened. We are hopeful that with so many talented scientists working in unison toward a common goal, we will have many positive outcomes."
As part of the Parker Institute, Dana-Farber will have access to innovative tools, resources and services. They include clinical trial management, bioinformatics and data analysis, and intellectual property management to help drive the research forward.
"We are thrilled to have our colleagues and collaborators from the Dana-Farber Cancer Institute joining the Parker Institute," said Jedd Wolchok, M.D., Ph.D., Parker Institute center director at Memorial Sloan Kettering Cancer Center. "The Parker Institute was not created to solely include a set number of institutions; rather, it's overarching goal is to integrate the best efforts of the most outstanding scientists and physicians in the field of cancer immunotherapy. Together, our aim is to discover and investigate the most innovative means to use the power of the immune system to control cancer."
About the Parker Institute for Cancer Immunotherapy The Parker Institute for Cancer Immunotherapy (http://www.parkerici.org/) brings together the best scientists, clinicians and industry partners to build a smarter and more coordinated cancer immunotherapy research effort.
The Parker Institute is an unprecedented collaboration between the country's leading immunologists and cancer centers, including Memorial Sloan Kettering Cancer Center, Stanford Medicine, the University of California, Los Angeles, the University of California, San Francisco, the University of Pennsylvania and The University of Texas MD Anderson Cancer Center. The Parker Institute network also includes more than 40 industry and nonprofit partners, more than 60 labs and more than 300 of the nation's top researchers focused on treating the deadliest cancers.
The goal is to accelerate the development of breakthrough immune therapies capable of turning most cancers into curable diseases. The institute was created through a $250 million grant from The Parker Foundation.
About Dana-Farber Cancer Institute From achieving the first remissions in childhood cancer with chemotherapy in 1948, to developing the very latest new therapies, Dana-Farber Cancer Institute is one of the world's leading centers of cancer research and treatment. It is the only center ranked in the top 4 of U.S. News and World Report's Best Hospitals for both adult and pediatric cancer care.
Dana-Farber sits at the center of a wide range of collaborative efforts to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber/Brigham and Women's Cancer Center (http://www.youhaveus.org/) provides the latest in cancer care for adults; Dana-Farber/Boston Children's Cancer and Blood Disorders Center (http://www.danafarberbostonchildrens.org/) for children. The Dana-Farber/Harvard Cancer Center (http://www.dfhcc.harvard.edu/) unites the cancer research efforts of five Harvard academic medical centers and two graduate schools, while Dana-Farber Community Cancer Care (http://www.dana-farber.org/About-Us/Satellite-Locations/Dana-Farber-Co...) provides high quality cancer treatment in communities outside Boston's Longwood Medical Area.
Dana-Farber is dedicated to a unique, 50/50 balance between cancer research and care, and much of the Institute's work is dedicated to translating the results of its discovery into new treatments for patients locally and around the world.
View original content with
multimedia:http://www.prnewswire.com/news-releases/dana-farber-cancer-institute-j...
SOURCE Parker Institute for Cancer Immunotherapy
Parker Institute for Cancer Immunotherapy, Anna Prince, aprince@parkerici.org, (415) 930-4328; Dana-Farber Cancer Institute, Brendan Monahan, BrendanJ_Monahan@DFCI.HARVARD.EDU, (617) 632-5653
US NIH, 11 drugmakers partner to accelerate cancer therapy research - Reuters News
12-Oct-2017 18:27:28
Adds advisory: updates with comments from news conference, byline
By Julie Steenhuysen
Oct 12 (Reuters) - The Trump Administration threw its support behind a public-private partnership with 11 drug companies to advance a new class of drugs that uses the body's immune system to fight cancer.
The five-year collaboration is part of the Cancer Moonshot, a program started during the Obama administration and led by former Vice President Joe Biden, whose son Beau died of brain cancer.
The Partnership for Accelerating Cancer Therapies or PACT will devote $215 million to identify and test chemical signatures in the body that will help predict which patients will benefit from cancer immunotherapy.
Drug industry partners include AbbVie ABBV.N, Roche Holding AG ROG.S and Bristol-Myers Squibb BMY.N, whose drug Opdivo works by enlisting the body's defenses to fight tumors.
Merck & Co Inc MRK.N, whose Keytruda leads the fast-expanding field of immunotherapies, is not involved.
In a Thursday press conference announcing the collaboration, Reed Cordish, who heads the Office of American Innovation, an initiative led by President Donald Trump's son-in-law Jared Kushner, said the program represents the "type of collaboration and partnership between the private sector and government that this administration is trying to foster across many sectors."
Eric Hargan, the newly tapped Acting Secretary for the Department of Health and Human Services, told reporters: "Under President Trump, we are going to continue making significant investments in cancer cures. Advancing great American medicine and science is a top, top priority for this administration."
Plans for the partnership began two years ago under the leadership of Dr. Francis Collins, director of the National Institutes of Health. Collins said the group will work to explain why cancer immunotherapies, which have transformed treatment for melanoma, leukemia and some other cancers, do not work for more patients.
"By standardizing and validating biomarkers for immunotherapy while also developing and exploring new biomarkers, we hope to advance rapidly toward a new future of precision oncology that benefits all patients," Collins told the briefing.
Pfizer Inc PFE.N, Johnson & Johnson JNJ.N, Amgen Inc AMGN.O, Celgene Corp CELG.O, Gilead Sciences Inc GILD.O and GlaxoSmithKline Plc GSK.L are part of the effort, NIH said.
The 11 partners would contribute up to $55 million, while NIH would add about $160 million, based on availability of funds.
The partnership will be managed by the Foundation for the National Institutes of Health.
(Editing by James Dalgleish)
Clinical News Roundup: FDA Says Clinical Trials System Is Broken
https://www.clinicalleader.com/doc/clinical-news-roundup-fda-says-clinical-trials-system-is-broken-0001
The role of T-cell immunoglobulin mucin-3 and its ligand galectin-9 in antitumor immunity and cancer immunotherapy
AuthorsAuthors and affiliations
Riyao Yang1
Mien-Chie Hung123Email author1.Department of Molecular and Cellular OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA2.Center for Molecular Medicine and Graduate Institute of Biomedical SciencesChina Medical UniversityTaichungChina3.Department of BiotechnologyAsia UniversityTaichungChina
https://link.springer.com/article/10.1007/s11427-017-9176-7
Prognostic implications and procoagulant activity of phosphatidylserine exposure of blood cells and microparticles in patients with atrial fibrillation treated with pulmonary vein isolation
October 11, 2017
https://www.spandidos-publications.com/10.3892/mmr.2017.7763
I know, that we know nothing.
I think that it has nothing to do with PPHM BUT: it has something to do with PS.
BIRGE!
The Procoagulant Activity of Apoptotic Cells Is Mediated by Interaction with Factor XII.
Yang A1, Chen F1, He C1, Zhou J1,2, Lu Y3, Dai J2,4, Birge RB5, Wu Y1,2.
Author information
1Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, United States.Department of Pathology and Laboratory Medicine, Rutgers University-New Jersey Medical School, Newark, NJ, United States.Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University-New Jersey Medical School, Newark, NJ, United States.
Abstract
Apoptotic cells, by externalizing phosphatidylserine (PS) as a hallmark feature, are procoagulant. However, the mechanism by which apoptotic cells activate coagulation system remains unknown. Intrinsic coagulation pathway is initiated by coagulation factor XII (FXII) of contact activation system. The purpose of this study was to determine whether FXII is involved in procoagulant activity of apoptotic cells. Using western blotting and chromogenic substrate assay, we found that incubation with apoptotic cells, but not with viable cells, resulted in rapid cleavage and activation of FXII in the presence of prekallikrein and high molecular weight kininogen (HK), other two components of contact activation system. As detected by flow cytometry, FXII bound to apoptotic cells in a concentration-dependent manner, which was inhibited by annexin V and PS liposome. Direct association of FXII with PS was confirmed in a surface plasmon resonance assay. Clotting time of FXII-deficient plasma induced by apoptotic cells was significantly prolonged, which was fully reversed by replenishment with FXII. Corn trypsin inhibitor, a FXII inhibitor, completely prevented apoptotic cells-induced intrinsic tenase complex formation. Consistently, apoptotic cells significantly increased thrombin production in normal plasma, which was not affected by an inhibitory anti-tissue factor antibody. However, blocking of PS by annexin V, inhibition of FXII, or the deficiency of FXII suppressed apoptotic cells-induced thrombin generation. Addition of purified FXII to FXII-deficient plasma recovered thrombin generation to the normal plasma level. In conclusion, FXII binds to apoptotic cells via PS and becomes activated, thereby constituting a novel mechanism mediating the procoagulant activity of apoptotic cells.
https://www.ncbi.nlm.nih.gov/pubmed/28993777
RONIN TRADING AND SW INVESTMENT MANAGEMENT ANNOUNCE ADDITIONAL NOMINATION TO BOARD OF PEREGRINE PHARMACEUTICALS
PRN
10/10/2017 6:59 PM
Ronin Trading and SW Investment Management Announce Additional Nomination to Board of Peregrine PharmaceuticalsBiotech Industry Veteran James (Jamie) J. Egan Joins Slate of Four Highly Qualified Candidates for Election at Upcoming 2017 Annual MeetingRonin Calls on Peregrine to Hold 2017 Annual Meeting without Further Delay
PR Newswire
CHICAGO, Oct. 10, 2017
CHICAGO, Oct. 10, 2017 /PRNewswire/ -- Ronin Trading, LLC and SW Investment Management LLC (together with the other participants in their solicitation, "Ronin" or "we"), collectively the second largest stockholder of Peregrine Pharmaceuticals, Inc. ("Peregrine" or the "Company") (NASDAQ:PPHM), with aggregate beneficial ownership of approximately 8.9% of the Company's outstanding shares of common stock, today issued the following statement with respect to Peregrine.
We are excited to announce our additional nomination of James (Jamie) J. Egan, a 30-year biotech veteran, for election to Peregrine's Board of Directors (the "Board") at the Company's 2017 annual meeting of stockholders (the "2017 Annual Meeting"). We believe Mr. Egan's deep understanding of antibodies, history of senior operations roles at reputable companies in the biotech industry, and proven ability to execute large deals with major pharmaceutical firms make him ideally suited for the Board and a great complement to our previously announced slate of nominees (Gregory P. Sargen, Brian W. Scanlan and Saiid Zarrabian). Mr. Egan's qualifications are discussed in greater detail below.
Ronin has put forth a slate of highly qualified candidates that we believe are capable of delivering stockholder value. Therefore, we are extremely frustrated that the Board continues to needlessly delay the 2017 Annual Meeting, an action that we believe benefits insiders at the expense of stockholders. It has been over ten weeks since Peregrine announced its intention to expand the size of the Board "from four to up to seven members through the addition of new highly-qualified independent directors," yet incredibly, the Board still has not announced a single independent candidate for its slate of nominees. Stockholders should not be punished for the Board's inability to identify qualified independent directors. Furthermore, we are dismayed that Peregrine's first new director candidate, Dr. Roger Lias, is a Company insider rather than an independent member. Not only is it inappropriate for two Company insiders to serve on the Board, but this appointment directly contradicts Peregrine's own statement about adding "independent" directors. We feel these actions are yet more evidence of the extraordinarily poor corporate governance practices at the Company and highlight the need for an overhaul of Peregrine's leadership.
Considering that Peregrine's past 15 annual meetings were held in October, it is blatantly obvious to us that the Company is stalling as a means to entrench the incumbents and insulate them from the will of Peregrine's stockholders. To the extent the Company fails to promptly call the 2017 Annual Meeting, we intend to file suit in accordance with Delaware law to compel the holding of the meeting so we can continue this process of change.
James J. Egan ("Jamie") currently serves as a strategic advisor to Numab AG, a Swiss biotech company that develops antibody-based therapeutics. From 2009 – 2012, Jamie was the Chief Operating Officer of Sucampo Pharmaceuticals, Inc., a publicly-traded global pharmaceutical company, during which time he worked closely with the company's manufacturing partners. Prior to that, Mr. Egan served as Chief Business Officer of ESBATech AG, a privately held Swiss biotechnology company, from 2006 until its acquisition by Alcon S.A. for $589 million in 2009, which Mr. Egan facilitated. From 2001 – 2006, Jamie was Senior VP of Licensing and Corporate Development for biopharmaceutical company Idenix Pharmaceuticals, Inc. ("Idenix"), where he played an instrumental role in Novartis AG's $255 million investment in the company as part of a strategic alliance that allowed Idenix to go public in 2004. Idenix was later acquired by Merck & Co. in 2014 for nearly $3.9 billion. Mr. Egan has also held senior operations roles at pharmaceutical company G.D. Searle & Co. and global healthcare company Abbott Laboratories in the 1980's and 1990's. Prior to becoming a biotech executive, Mr. Egan was a foreign services officer at the US embassy in Tokyo and an attorney with the Department of Justice. Mr. Egan is fluent in Japanese.
CERTAIN INFORMATION CONCERNING THE PARTICIPANTS
Ronin Trading, LLC, together with the other participants named herein (collectively, "Ronin"), has filed a preliminary proxy statement and an accompanying proxy card with the Securities and Exchange Commission ("SEC") to be used to solicit votes for the election of its slate of four highly qualified director nominees at the 2017 annual meeting of stockholders Peregrine Pharmaceuticals, Inc., a Delaware corporation (the "Company").
RONIN STRONGLY ADVISES ALL STOCKHOLDERS OF THE COMPANY TO READ THE PROXY STATEMENT AND OTHER PROXY MATERIALS AS THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION. SUCH PROXY MATERIALS WILL BE AVAILABLE AT NO CHARGE ON THE SEC'S WEB SITE AT HTTP://WWW.SEC.GOV (HTTP://WWW.SEC.GOV). IN ADDITION, THE PARTICIPANTS IN THIS PROXY SOLICITATION WILL PROVIDE COPIES OF THE PROXY STATEMENT WITHOUT CHARGE, WHEN AVAILABLE, UPON REQUEST.
The participants in the solicitation are Ronin Trading, LLC ("Ronin Trading"), John S. Stafford, III, SWIM Partners LP ("SWIM Partners"), SW Investment Management LLC ("SW Management"), Stephen White, James J. Egan, Gregory P. Sargen, Brian W. Scanlan and Saiid Zarrabian.
As of the date hereof, Ronin Trading directly beneficially owned 3,310,652 shares of the Company's common stock, $0.001 par value per share ("Common Stock"), including 137,260 shares of Common Stock that may be acquired upon the conversion of 115,299 shares of the Company's 10.50% Series E Convertible Preferred Stock, $0.001 par value per share ("Series E Preferred Stock"). Mr. Stafford, as the Manager of Ronin Trading, may be deemed to beneficially own the 3,310,652 shares of Common Stock beneficially owned directly by Ronin Trading. As of the date hereof, SWIM Partners directly beneficially owned 510,333 shares of Common Stock, including 10,333 shares of Common Stock that may be acquired upon the conversion of 8,680 shares of Series E Preferred Stock. As of the date hereof, an account separately managed by SW Management (the "SW Account") held 203,714 shares of Common Stock, including 3,714 shares of Common Stock that may be acquired upon the conversion of 3,120 shares of Series E Preferred Stock. SW Management, as the general partner and investment adviser of SWIM Partners and the investment adviser of the SW Account, may be deemed to beneficially own the 714,047 shares of Common Stock beneficially owned in the aggregate by SWIM Partners and held in the SW Account. Mr. White, as the Manager of SW Management, may be deemed to beneficially own the 714,047 shares of Common Stock beneficially owned in the aggregate by SWIM Partners and held in the SW Account. As of the date hereof, Messrs. Egan, Sargen, Scanlan and Zarrabian did not beneficially own any securities of the Company.
Investor Contact:
Stephen White
SW Investment Management LLC
(312) 765-7033
View original
content:http://www.prnewswire.com/news-releases/ronin-trading-and-sw-investment-management-announce-additional-nomination-to-board-of-peregrine-pharmaceuticals-300534063.html
SOURCE Ronin Trading, LLC and SW Investment Management LLC
Copyright (c) 2017 PR Newswire Association,LLC. All Rights Reserved.
nPn2gHN8Ta
© Thomson Reuters 2017. All rights reserved.
Published OnlineFirst June 25, 2015
Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade
Keep cool - it´s from 2015!
Raymond J. KelleherJr1, Sathy Balu-Iyer2, Jenni Loyall1, Anthony J. Sacca1,
Gautam N. Shenoy1, Peng Peng1,Vandana Iyer2, Anas M. Fathallah2,
Charles S. Berenson3, Paul K.Wallace4, Joseph Tario4, Kunle Odunsi5, and
Richard B. Bankert1
https://pdfs.semanticscholar.org/d73b/c3627081187f1b713573e60ac3076b6600d4.pdf
SITC 2017 Abstract Titles – Combination Therapy
November 8-12
P262
Phosphatidylserine targeting antibody in combination with tumor radiation and immune checkpoint blockade promotes anti-tumor activity in mouse B16 melanoma
GLIIFCA 2017 Presentation Abstracts - September 2017
Tumor-Associated Exosomes Represent a Reversible T Cell Checkpoint
Gautam Shenoy (University at Buffalo, Buffalo, NY)
[]{#flow-cytometry-and-immunotherapy-histori .anchor}T cells in tumor microenvironments are rendered hyporesponsive to activation by a combination of cellular and acellular factors. The identification of these immunosuppressive factors would allow for designing strategies to block them and ultimately enhance patients’ anti-tumor immune responses by re-activating these tumor-associated T cells. We have identified membrane encapsulated extracellular vesicles with the size, biophysical and compositional properties that are characteristic of exosomes, in ascites fluids as well as solid tumors derived from ovarian cancer patients. T cells briefly pulsed with these tumor-associated exosomes during activation rapidly inhibit multiple different activation endpoints including the translocation of NFkB and NFAT into the nucleus, the upregulation of CD69 and CD107a, production of cytokines and cell proliferation. The inhibition occurs without loss of cell viability, and coincidentally with the binding and internalization of these exosomes. This exosome-mediated inhibition of T cells has been determined to be transient and reversible. We demonstrate that the tumor-associated exosome-induced T cell signaling arrest is dependent upon phosphatidylserine (PS), as a blockade of PS with anti-PS antibodies significantly reverses the inhibitory activity of the exosomes. We also report that the inhibitory activity is overcome by the addition of diacylglycerol kinase inhibitors, suggesting a possible mechanism for the T cell inhibition. We conclude that exosomes present within ovarian tumor microenvironments represent a novel T cell checkpoint, and represent a potentially viable target to block and thereby enhance anti-tumor immune responses in ovarian cancer patients.
For those who are interested in TNBC:
Protein and chemotherapy profiling of extracellular vesicles harvested from therapeutic induced senescent triple negative breast cancer cells
Published online 9 October 2017
http://www.nature.com/oncsis/journal/v6/n10/full/oncsis201782a.html?foxtrotcallback=true
Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles.
Durcin M1,2, Fleury A1, Taillebois E1, Hilairet G1, Krupova Z3,4, Henry C5, Truchet S2, Trötzmüller M6,7, Köfeler H6,7, Mabilleau G8,Hue O2, Andriantsitohaina R1, Martin P3, Le Lay S1.
Author information
1INSERM U1063, Oxidative stress and metabolic pathologies, Angers University, Pointe à Pitre, France.Adaptation to Tropical Climate and Exercise Laboratory, EA3596, University of the French West Indies, Pointe-à-Pitre, Guadeloupe, France.GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.MICALIS Institute, INRA, AgroParisTech, PAPPSO, Université Paris-Saclay, Jouy-en-Josas, France.Center for Medical Research, Medical University of Graz, Graz, Austria.SCIAM, Angers University, Angers, France.
Abstract
Extracellular vesicles (EVs) are biological vectors that can modulate the metabolism of target cells by conveying signalling proteins and genomic material. The level of EVs in plasma is significantly increased in cardiometabolic diseases associated with obesity, suggesting their possible participation in the development of metabolic dysfunction. With regard to the poor definition of adipocyte-derived EVs, the purpose of this study was to characterise both qualitatively and quantitatively EVs subpopulations secreted by fat cells. Adipocyte-derived EVs were isolated by differential centrifugation of conditioned media collected from 3T3-L1 adipocytes cultured for 24 h in serum-free conditions. Based on morphological and biochemical properties, as well as quantification of secreted EVs, we distinguished two subpopulations of adipocyte-derived EVs, namely small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs). Proteomic analyses revealed that lEVs and sEVs exhibit specific protein signatures, allowing us not only to define novel markers of each population, but also to predict their biological functions. Despite similar phospholipid patterns, the comparative lipidomic analysis performed on these EV subclasses revealed a specific cholesterol enrichment of the sEV population, whereas lEVs were characterised by high amounts of externalised phosphatidylserine. Enhanced secretion of lEVs and sEVs is achievable following exposure to different biological stimuli related to the chronic low-grade inflammation state associated with obesity. Finally, we demonstrate the ability of primary murine adipocytes to secrete sEVs and lEVs, which display physical and biological characteristics similar to those described for 3T3-L1. Our study provides additional information and elements to define EV subtypes based on the characterisation of adipocyte-derived EV populations. It also underscores the need to distinguish EV subpopulations, through a combination of multiple approaches and markers, since their specific composition may cause distinct metabolic responses in recipient cells and tissues.
https://www.ncbi.nlm.nih.gov/pubmed/28473884?dopt=Abstract
Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor.
Wu X1, Zhang LS1, Toombs J2,3, Kuo YC3,4, Piazza JT1, Tuladhar R1, Barrett Q1, Fan CW1, Zhang X3,4, Walensky LD5,6, Kool M7,8,Cheng SY9,10, Brekken R2,3, Opferman JT11, Green DR12, Moldoveanu T13,14, Lum L1.
Author information
Abstract
Direct interactions between pro- and anti-apoptotic BCL-2 family members form the basis of cell death decision-making at the outer mitochondrial membrane (OMM). Here we report that three anti-apoptotic BCL-2 proteins (MCL-1, BCL-2 and BCL-XL) found untethered from the OMM function as transcriptional regulators of a prosurvival and growth program. Anti-apoptotic BCL-2 proteins engage a BCL-2 homology (BH) domain sequence found in SUFU (suppressor of fused), a tumour suppressor and antagonist of the GLI DNA-binding proteins. BCL-2 proteins directly promote SUFU turnover, inhibit SUFU-GLI interaction, and induce the expression of the GLI target genes BCL-2, MCL-1 and BCL-XL. Anti-apoptotic BCL-2 protein/SUFU feedforward signalling promotes cancer cell survival and growth, and can be disabled with BH3 mimetics-small molecules that target anti-apoptotic BCL-2 proteins. Our findings delineate a chemical strategy for countering drug resistance in GLI-associated tumours and reveal unanticipated functions for BCL-2 proteins as transcriptional regulators.
http://www.nature.com/ncb/journal/v19/n10/full/ncb3616.html?foxtrotcallback=true
Insights into the Cytoadherence Phenomenon of Plasmodium vivax: The Putative Role of Phosphatidylserine.
Totino PR1, Lopes SC2.
Author information
Abstract
Plasmodium vivax is the most geographically widespread and the dominant human malaria parasite in most countries outside of sub-Saharan Africa and, although it was classically recognized to cause benign infection, severe cases and deaths caused by P. vivax have remarkably been reported. In contrast to Plasmodium falciparum, which well-known ability to bind to endothelium and placental tissue and form rosettes is related to severity of the disease, it has been a dogma that P. vivax is unable to undergo cytoadherent phenomena. However, some studies have demonstrated that red blood cells (RBCs) infected by P. vivax can cytoadhere to host cells, while the molecules participating in this host-parasite interaction are still a matter of speculation. In the present overview, we address the evidences currently supporting the adhesive profile of P. vivax and, additionally, discuss the putative role of phosphatidylserine-a cell membrane phospholipid with cytoadhesive properties that has been detected on the surface of Plasmodium-parasitized RBCs.
https://www.ncbi.nlm.nih.gov/pubmed/28979260
Immunotherapy pioneer researching ways to use body's immune system to fight cancer - CNBC
https://www.cnbc.com/video/2017/10/05/immunotherapy-pioneer-researching-ways-to-use-bodys-immune-system-to-fight-cancer.html
Extracellular vesicles: how they interact with endothelium, potentially contributing to metastatic cancer cell implants.
Bern MM1.
Author information
Abstract
Extracellular vesicles (EV) are blebs of cellular membranes, which entrap small portions of subjacent cytosol. They are released from a variety of cells, circulate in the blood for an unknown length of time and come to rest on endothelial surfaces. They contribute to an array of physiologic pathways, the complexity of which is still being investigated. They contribute to metastatic malignant cell implants and tumor-related angiogenesis, possibly abetted by the tissue factor that they carry. It is thought that the adherence of the EV to endothelium is dependent upon a combination of their P-selectin glycoprotein ligand-1 and exposed phosphatidylserine, the latter of which is normally hidden on the inner bilayer of the intact cellular membrane. This manuscript reviews what is known about EV origins, their clearance from the circulation and how they contribute to malignant cell implants upon endothelium surfaces and subsequent tumor growth.
KEYWORDS:
Endothelium; Exosomes; Extracellular vesicles; Hypercoagulation; Metastatic carcinoma; Microparticles; P-selectin; P-selectin glycoprotein ligand 1; Tissue factor
https://www.ncbi.nlm.nih.gov/pubmed/28933058
Full text:
https://clintransmed.springeropen.com/articles/10.1186/s40169-017-0165-2
Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.
Ma R1,2, Xie R1,3, Yu C1, Si Y1,2, Wu X1, Zhao L1, Yao Z1, Fang S2, Chen H4, Novakovic V5, Gao C1, Kou J6, Bi Y7, Thatte HS8, Yu B2, Yang S9, Zhou J10, Shi J11,12.
Author information
Abstract
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or avß3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.
https://www.ncbi.nlm.nih.gov/pubmed/28694452
Wu X is working together with Brekken!
Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor.
Wu X1, Zhang LS1, Toombs J2,3, Kuo YC3,4, Piazza JT1, Tuladhar R1, Barrett Q1, Fan CW1, Zhang X3,4, Walensky LD5,6, Kool M7,8, Cheng SY9,10, Brekken R2,3, Opferman JT11, Green DR12, Moldoveanu T13,14, Lum L1.
Author information
Abstract
Direct interactions between pro- and anti-apoptotic BCL-2 family members form the basis of cell death decision-making at the outer mitochondrial membrane (OMM). Here we report that three anti-apoptotic BCL-2 proteins (MCL-1, BCL-2 and BCL-XL) found untethered from the OMM function as transcriptional regulators of a prosurvival and growth program. Anti-apoptotic BCL-2 proteins engage a BCL-2 homology (BH) domain sequence found in SUFU (suppressor of fused), a tumour suppressor and antagonist of the GLI DNA-binding proteins. BCL-2 proteins directly promote SUFU turnover, inhibit SUFU-GLI interaction, and induce the expression of the GLI target genes BCL-2, MCL-1 and BCL-XL. Anti-apoptotic BCL-2 protein/SUFU feedforward signalling promotes cancer cell survival and growth, and can be disabled with BH3 mimetics-small molecules that target anti-apoptotic BCL-2 proteins. Our findings delineate a chemical strategy for countering drug resistance in GLI-associated tumours and reveal unanticipated functions for BCL-2 proteins as transcriptional regulators.
Pro-necrotic Activity of Cationic Mastoparan Peptides in Human Glioblastoma Multiforme Cells Via Membranolytic Action.
Sep. 30, 2017
da Silva AMB1, Silva-Gonçalves LC1, Oliveira FA2, Arcisio-Miranda M3.
Author information
Abstract
Glioblastoma multiforme is the most common and lethal malignant brain tumor. Because of its complexity and heterogeneity, this tumor has become resistant to conventional therapies and the available treatment produces multiple side effects. Here, using multiple experimental approaches, we demonstrate that three mastoparan peptides-Polybia-MP1, Mastoparan X, and HR1-from solitary wasp venom exhibit potent anticancer activity toward human glioblastoma multiforme cells. Importantly, the antiglioblastoma action of mastoparan peptides occurs by membranolytic activity, leading to necrosis. Our data also suggest a direct relation between mastoparan membranolytic potency and the presence of negatively charged phospholipids like phosphatidylserine. Collectively, these data may warrant additional studies for mastoparan peptides as new agents for the treatment of glioblastoma multiforme brain tumor.
https://www.ncbi.nlm.nih.gov/pubmed/28965321
Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm.
Younan P1,2,3, Iampietro M1,2,3, Nishida A4, Ramanathan P1,2,3, Santos RI1,2,3, Dutta M4, Lubaki NM1,2,3, Koup RA5, Katze MG4,6,Bukreyev A7,8,2,3.
Author information
1Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.Galveston National Laboratory, The University of Texas Medical Branch, Galveston, Texas, USA.The University of Texas Medical Branch, Galveston, Texas, USA.Department of Microbiology, University of Washington, Seattle, Washington, USA.Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA alexander.bukreyev@utmb.edu.Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
Abstract
Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a "cytokine storm." Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1-/- mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1-/- mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine-Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4Hi CD3Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4+ T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4+ T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD.IMPORTANCE Ebola virus infection is characterized by a massive release of inflammatory mediators, which has come to be known as a cytokine storm. The severity of the cytokine storm is consistently linked with fatal disease outcome. Previous findings have demonstrated that specific T-cell subsets are key contributors to the onset of a cytokine storm. In this study, we investigated the role of Tim-1, a T-cell-receptor-independent trigger of T-cell activation. We first demonstrated that Tim-1-knockout (KO) mice survive lethal Ebola virus challenge. We then used a series of in vitro assays to demonstrate that Ebola virus directly binds primary T cells in a Tim-1-phosphatidylserine-dependent manner. We noted that binding induces a cytokine storm-like phenomenon and that blocking Tim-1-phosphatidylserine interactions reduces viral binding, T-cell activation, and cytokine production. These findings highlight a previously unknown role of Tim-1 in the development of a cytokine storm and "immune paralysis."
Copyright © 2017 Younan et al.
https://www.ncbi.nlm.nih.gov/pubmed/28951472
Targeting Phosphatidylserine with Calcium-dependent Protein-Drug Conjugates for the Treatment of Cancer.
Sep. 22 2017
Li R1, Chiguru S2, Li L2, Kim D3, Velmurugan R4, Kim D5, Devanaboyina SC1, Tian H6, Schroit A7, Mason R2, Ober RJ8, Ward ES9.
Author information
1Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center.Department of Radiology, University of Texas Southwestern Medical Center.Biomedical Engineering, Texas A&M University.Biomedical Engineering Graduate Program, University of Texas Southwestern Medical Center.Texas A&M University.China Pharmaceutical University.Department of Pharmacology, University of Texas Southwestern Medical Center.Department of Biomedical Engineering, Texas A&M University.Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center sally.ward@medicine.tamhsc.edu.
Abstract
In response to cellular stress, phosphatidylserine (PS) is exposed on the outer membrane leaflet of tumor blood vessels and cancer cells, motivating the development of PS-specific therapies. The generation of drug-conjugated PS-targeting agents represents an unexplored therapeutic approach, for which anti-tumor effects are critically dependent on efficient internalization and lysosomal delivery of the cytotoxic drug. In the current study, we have generated PS-targeting agents by fusing PS-binding domains to a human IgG1-derived Fc fragment. The tumor localization and pharmacokinetics of several PS-specific Fc fusions have been analyzed in mice and demonstrate that Fc-Syt1, a fusion containing the synaptotagmin 1 C2A domain, effectively targets tumor tissue. Conjugation of Fc-Syt1 to the cytotoxic drug, monomethyl auristatin E, results in a protein-drug conjugate (PDC) that is internalized into target cells and, due to the Ca²?-dependence of PS binding, dissociates from PS in early endosomes. The released PDC is efficiently delivered to lysosomes and has potent anti-tumor effects in mouse xenograft tumor models. Interestingly, whilst an engineered, tetravalent Fc-Syt1 fusion shows increased binding to target cells, this higher avidity variant demonstrates reduced persistence and therapeutic effects compared with bivalent Fc-Syt1. Collectively, these studies show that finely tuned, Ca²?-switched PS-targeting agents can be therapeutically efficacious.
Copyright ©2017, American Association for Cancer Research.
https://www.ncbi.nlm.nih.gov/pubmed/28939556
Avid Bioservices Expands Manufacturing Capabilities With Installation and Validation of Two MilliporeSigma Mobius® 2,000-Liter Single-Use Bioreactors in Its Myford Facility - GNW
25-Sep-2017 14:05
Bioreactors Now Online and Able to Meet Needs of Current and Future Clients
--
State-of-the-Art Myford Facility Features Industry-Leading Flexibility, Scalability and Ease-of-Use --
TUSTIN, Calif., Sept. 25, 2017 (GLOBE NEWSWIRE) -- Avid Bioservices, Inc., a wholly owned subsidiary of Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), today announced the successful installation and validation of two Mobius(®) 2,000-liter single-use bioreactors from MilliporeSigma in Avid’s Myford clinical and commercial manufacturing facility. The bioreactors are officially online and able to accommodate the growing demand for larger scale single-use bioreactors from current and future Avid clients. Avid has already secured customer commitments for a portion of the manufacturing capacity associated with the new bioreactors.
“We have been working diligently on the installation and validation of these new 2,000-liter bioreactors and are excited to now be in a position to launch the manufacturing activities that this state-of-the-art equipment enables. This enhancement of our capabilities is just the latest step in our ongoing efforts to expand and diversify our customer base,” said Roger Lias, Ph.D., president of Avid Bioservices. “Importantly, based on the modular design of our Myford facility, we have the ability to install one additional 2,000-liter bioreactor, allowing us to further accelerate the growth of the business.”
The newly installed 2,000-liter single-use bioreactors offer a range of important manufacturing advantages and efficiencies as compared to other equipment. Traditionally, biopharmaceutical companies used large stainless steel vessels in multi-story buildings, requiring substantial investment and rigorous setup. With single-use disposable equipment, customers get improved batch turnaround times, reduced risk of product cross-contamination, decreased capital costs and have less equipment to clean. Single-use technology helps accelerate customers’ molecules to market, improve productivity, and ensure supply continuity.
“MilliporeSigma’s Mobius(®) 2,000-liter single-use bioreactors are easy to use and play an integral role in Avid’s goal toward having a fully disposable biomanufacturing process,” said Andrew Bulpin, Head of Process Solutions at MilliporeSigma. “We look forward to continuing to work with companies around the world to bring their molecules to market and accelerate production of critical medicines.”
The 42,000 square foot Myford facility is designed with cutting-edge, single-use equipment to accommodate a fully disposable biomanufacturing process. A wide range of innovative features are incorporated into this new facility including monolithic modular clean rooms, dedicated support utilities for each key processing area, and the industry’s most advanced single-use production systems and flexible solutions. Uni-directional process flows separate personnel and materials and provide assurance that the design meets the most stringent regulatory requirements for commercial biologics API manufacturing.
About Avid Bioservices, Inc.
Avid Bioservices, a wholly owned subsidiary of Peregrine Pharmaceuticals, provides a comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With over 20 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, including 12 years of commercial manufacturing for products sold in 18 countries, Avid's services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, lot release and stability testing, regulatory strategy, submission and support. The company also provides a variety of process development activities, including cell line development and optimization, cell culture and feed optimization, analytical methods development, qualification/validation, process and product characterization. For more information about Avid, please visit www.avidbio.com.
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of patients by delivering high quality pharmaceutical products through its contract development and manufacturing organization (CDMO) services and through advancing and licensing its investigational immunotherapy and related products. Peregrine's in-house CDMO services, including cGMP manufacturing and development capabilities, are provided through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and third-party customers. The company is also working to evaluate its lead immunotherapy candidate, bavituximab, in combination with immune stimulating therapies for the treatment of various cancers, and developing its proprietary exosome technology for the detection and monitoring of cancer. For more information, please visit www.peregrineinc.com.
Contacts:
Kelly Pisarev Lord
Avid Bioservices, Inc.
(800) 987-8256
Stephanie Diaz (Investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
GlobeNewswire, Inc. 2017
Apoptotic Bodies Elicit Gas6-mediated Migration of AXL-expressing Tumor Cells.
Zweemer AJ1, French CB2, Mesfin J3, Gordonov S3, Meyer AS4, Lauffenburger DA5.
Author information
Abstract
Metastases are a major cause of cancer mortality. AXL, a receptor tyrosine kinase (RTK) aberrantly expressed in many tumors, is a potent oncogenic driver of metastatic cell motility and has been identified as broadly relevant in cancer drug resistance. Despite its frequent association with changes in cancer phenotypes, the precise mechanism leading to AXL activation is incompletely understood. In addition to its ligand growth arrest specific-6 (Gas6), activation of AXL requires the lipid moiety phosphatidylserine (PS). PS is only available to mediate AXL activation when it is externalized on cell membranes, an event that occurs during certain physiologic processes such as apoptosis. Here it is reported that exposure of cancer cells to PS-containing vesicles, including synthetic liposomes and apoptotic bodies, contributes to enhanced migration of tumor cells via a PS-Gas6-AXL signaling axis. These findings suggest that anti-cancer treatments that induce fractional cell killing enhance the motility of surviving cells in AXL-expressing tumors, which may explain the widespread role of AXL in limiting therapeutic efficacy.
IMPLICATIONS:
This study demonstrates that motility behavior of AXL-expressing tumor cells can be elicited by Gas6-bearing apoptotic bodies generated from tumor treatment with therapeutics that produce killing of a portion of the tumor cells present but not all, hence generating potentially problematic invasive and metastatic behavior of the surviving tumor cells.
Copyright ©2017, American Association for Cancer Research.
https://www.ncbi.nlm.nih.gov/pubmed/?term=phosphatidylserine
Sorry bfiest, but that´s your interpretation - that´s not what CP said/wrote. IMO
Sorry - I have no link for that - it´s from Reuters
Eastern Capital:
Security Name Value Held ($) Position % Portfolio % Outstanding Filing Date
Alnylam Pharmaceuticals Inc 222.703.112,37 3.802.341,00 56,81% 4,14% 25-02-2016
Spectrum Pharmaceuticals Inc 36.050.906,27 4.737.307,00 9,20% 5,61% 17-04-2017
Cytokinetics Inc 30.568.757,00 2.883.845,00 7,80% 5,37% 28-02-2017
Exelixis Inc 26.308.777,04 7.227.686,00 6,71% 2,46% 11-02-2016
Resverlogix Corp 24.643.413,53 22.183.287,00 6,29% 19,35% 20-06-2017
Peregrine Pharmaceuticals Inc 11.709.267,30 3.777.183,00 2,99% 8,38% 25-08-2017
Ibio Inc 9.981.475,20 33.744.000,00 2,55% 36,35% 02-08-2017
Vericel Corp 8.330.764,40 2.975.273,00 2,13% 9,06% 10-03-2017
TapImmune Inc 7.583.335,50 2.333.334,00 1,93% 22,97% 25-08-2017
Verastem Inc 4.073.463,99 1.967.857,00 1,04% 5,32% 15-03-2017
XOMA Corp 3.980.819,20 261.896,00 1,02% 3,45% 22-02-2016
Cyclacel Pharmaceuticals Inc 3.640.998,48 2.167.261,00 0,93% 19,01% 10-08-2017
Synlogic Inc 1.689.297,40 159.820,00 0,43% 0,98% 31-05-2017
Next DART-stock is up - ALNY +31%
Eastern Cap. 4,14% ownership or 3.80M shares
Avid Bioservices to Exhibit at 2017 BioProcess International Conference & Exhibition - GNW
19-Sep-2017 14:05
TUSTIN, Calif., Sept. 19, 2017 (GLOBE NEWSWIRE) -- Avid Bioservices, Inc., a wholly owned subsidiary of Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), today announced that the company will exhibit at the upcoming 2017 BioProcess International Conference & Exhibition, being held September 25-28, 2017 in Boston, MA. Avid will host a corporate booth (#918) in the conference’s exhibit hall, where it will showcase the company’s comprehensive range of process development, analytical development, testing and characterization services and high quality cGMP clinical and commercial biologics manufacturing of monoclonal antibodies and recombinant proteins. Avid representatives attending the conference will include newly appointed president Roger Lias, Ph.D., and Steven King, who is stepping down from his role as president of Avid, but remaining as president and chief executive officer of Peregrine.
At BioProcess International, the Avid team will be able to discuss the company’s innovative processes for generating a broad range of biopharmaceutical product types including monoclonal antibodies, highly-glycosylated recombinant proteins and enzymes, among others. As part of its exhibit, the company will provide a virtual tour of the company’s 42,000 square foot state-of-the-art Myford manufacturing facility, which is designed for late-stage clinical and commercial biologics manufacturing. As previously announced, the company will soon be ready to offer new larger scale capacity from the two recently installed 2,000-liter, single-use bioreactors at the Myford facility.
The Myford facility is designed with cutting-edge, single-use equipment to accommodate a fully disposable biomanufacturing process. A wide range of innovative features are incorporated into this new facility including monolithic modular clean rooms, dedicated support utilities for each key processing area, and the industry’s most advanced single-use production systems and flexible solutions. Uni-directional process flows separate personnel and materials and provide assurance that the design meets the most stringent regulatory requirements for commercial biologics API manufacturing.
For more information on the 2017 BioProcess International Conference & Exhibition, please visit:
https://lifesciences.knect365.com/bioprocessinternational/.
Avid Bioservices was established as Peregrine’s internal biologics manufacturing and development group, and began formal operations in January 2002. The company has grown from an internal support operation to a full service CDMO that manufactures bulk drug substance for products that are approved and marketed in over 18 countries by leading biopharma companies, including the US and EU. Avid was recently recognized as a leading CDMO by Life Science Leader as a recipient of multiple 2017 Contract Manufacturing Leadership Awards for Quality, Reliability, Capabilities, Expertise and Compatibility. The company has an outstanding regulatory inspection history, including 12 years of commercial manufacturing and state-of-the-art cGMP manufacturing facilities.
About Avid Bioservices, Inc.
Avid Bioservices, a wholly owned subsidiary of Peregrine Pharmaceuticals, provides a comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With over 20 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, including 12 years of commercial manufacturing for products sold in 18 countries, Avid's services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, lot release and stability testing, regulatory strategy, submission and support. The company also provides a variety of process development activities, including cell line development and optimization, cell culture and feed optimization, analytical methods development, qualification/validation, process and product characterization. For more information about Avid, please visit www.avidbio.com.
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of patients by delivering high quality pharmaceutical products through its contract development and manufacturing organization (CDMO) services and through advancing and licensing its investigational immunotherapy and related products. Peregrine's in-house CDMO services, including cGMP manufacturing and development capabilities, are provided through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and third-party customers. The company is also working to evaluate its lead immunotherapy candidate, bavituximab, in combination with immune stimulating therapies for the treatment of various cancers, and developing its proprietary exosome technology for the detection and monitoring of cancer. For more information, please visit www.peregrineinc.com.
Contacts:
Kelly Pisarev Lord
Avid Bioservices, Inc.
(800) 987-8256
Stephanie Diaz (Investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
GlobeNewswire, Inc. 2017
Loss of Tmem30a leads to photoreceptor degeneration.
2017 Aug. 24
Zhang L1,2, Yang Y1,2, Li S1,3, Zhang S1, Zhu X1, Tai Z1,3, Yang M1,3, Liu Y1,2, Guo X4, Chen B4, Jiang Z1, Lu F5,6, Zhu X7,8,9,10.
Author information
Abstract
Phosphatidylserine (PS) is asymmetrically distributed between the outer and inner leaflets of the plasma membrane in eukaryotic cells. PS asymmetry on the plasma membrane depends on the activities of P4-ATPases, and disruption of PS distribution can lead to various disease conditions. Folding and transporting of P4-ATPases to their cellular destination requires the ß subunit TMEM30A proteins. However, the in vivo functions of Tmem30a remain unknown. To this end, we generated retinal-specific Tmem30a-knockout mice to investigate its roles in vivo for the first time. Our data demonstrated that loss of Tmem30a in mouse cone cells leads to mislocalization of cone opsin, loss of photopic electroretinogram (ERG) responses and loss of cone cells. Mechanistically, Tmem30a-mutant mouse embryonic fibroblasts (MEFs) exhibited diminished PS flippase activity and increased exposure of PS on the cell surface. The broad loss of Tmem30a in adult mice led to a reduced scotopic photoresponse, mislocalization of ATP8A2 to the inner segment and cell body, and increased apoptosis in the retina. Our data demonstrated novel essential roles of Tmem30a in the retina.
https://www.ncbi.nlm.nih.gov/pubmed/28839191
Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment.
Yeku OO1, Purdon TJ1, Koneru M1, Spriggs D1, Brentjens RJ2.
Author information
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA.Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA. brentjer@mskcc.org.
Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy for the management of solid tumor malignancies. In ovarian cancer, this is in part due to an immunosuppressive cytokine and cellular tumor microenvironment which suppresses adoptively transferred T cells. We engineered an armored CAR T cell capable of constitutive secretion of IL-12, and delineate the mechanisms via which these CAR T cells overcome a hostile tumor microenvironment. In this report, we demonstrate enhanced proliferation, decreased apoptosis and increased cytotoxicity in the presence of immunosuppressive ascites. In vivo, we show enhanced expansion and CAR T cell antitumor efficacy, culminating in improvement in survival in a syngeneic model of ovarian peritoneal carcinomatosis. Armored CAR T cells mediated depletion of tumor associated macrophages and resisted endogenous PD-L1-induced inhibition. These findings highlight the role of the inhibitory microenvironment and how CAR T cells can be further engineered to maintain efficacy.
https://www.ncbi.nlm.nih.gov/pubmed/28874817
Facts and Hopes in Immunotherapy of Lymphoma and Myeloma.
Pianko MJ1, Moskowitz AJ2, Lesokhin AM3.
Author information
1Medicine, Memorial Sloan-Kettering Cancer Center.Lymphoma Service, Memorial Sloan-Kettering Cancer Center.Medicine, Memorial Sloan-Kettering Cancer Center lesokhia@mskcc.org.
Abstract
Immune checkpoint blockade has driven a revolution in modern oncology, and robust drug development of immune checkpoint inhibitors is underway in both solid tumors and hematologic malignancies. High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biologic sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL. There are also preliminary data suggesting antitumor efficacy of PD-1 inhibitors used in combination with immunomodulatory drugs in multiple myeloma (MM), and effects of novel monoclonal antibody therapies on the tumor microenvironment may lead to synergy with checkpoint blockade. Although immune checkpoint inhibitors are generally well-tolerated, clinicians must use caution and remain vigilant when treating patients with these agents in order to identify immune related toxicities and prevent treatment-related morbidity and mortality. Autologous stem cell transplant is a useful tool for treatment of hematologic malignancies and has potential as a platform for use of immune checkpoint inhibitors. An important safety signal has emerged surrounding the risk of graft-versus-host-disease (GVHD) associated with use of PD-1 inhibitors before and after allogeneic stem cell transplant. We aim to discuss the facts known to date in the use of immune checkpoint inhibitors for patients with lymphoid malignancies, and discuss our hopes for expanding the benefits of immunotherapy to patients in the future.
Copyright ©2017, American Association for Cancer Research.
https://www.ncbi.nlm.nih.gov/pubmed/28899972
The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls.
September 2017
Hellum M1,2, Franco-Lie I3, Øvstebø R2, Hauge T1,3, Henriksson CE1,2.
Author information
Abstract
Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine(PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP). Thrombin generation was measured by the calibrated automated thrombogram. The impact of corn trypsin inhibitor (CTI), anti-tissue factor pathway inhibitor (TFPI) antibodies and phospholipids was described. Antibodies against TF were used to assess TF-dependency, and MV-bound PS activity was measured with the Zymuphen MP-activity kit. MVs from the pancreatic cancer patients displayed higher thrombin generation and higher PS-activity than MVs from the healthy control group, while TF-dependency was observed in only 1 out of 13 patient samples. Adequate thrombin generation-curves were only achieved when CTI was omitted and anti-TFPI antibodies were added to PNP prepared in low contact-activating tubes. Addition of phospholipids reduced the significant differences between the two groups, and should be omitted. This modified thrombin generation assay could be useful for measurement of procoagulant circulating MVs, allowing the contribution from MVs affecting both the intrinsic and the extrinsic pathway to be measured.
https://www.ncbi.nlm.nih.gov/pubmed/28910348