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In 12 months or so.
imo
Chemical imaging of aggressive basal cell carcinoma using time-of-flight secondary ion mass spectrometry.
Munem M1, Zaar O2, Dimovska Nilsson K1, Neittaanmäki N3, Paoli J2, Fletcher JS1.
Author information
Abstract
A set of basal cell carcinoma samples, removed by Mohs micrographic surgery and pathologically identified as having an aggressive subtype, have been analyzed using time-of-flight secondary ion mass spectrometry (SIMS). The SIMS analysis employed a gas cluster ion beam (GCIB) to increase the sensitivity of the technique for the detection of intact lipid species. The GCIB also allowed these intact molecular signals to be maintained while surface contamination and delocalized chemicals were removed from the upper tissue surface. Distinct mass spectral signals were detected from different regions of the tissue (epidermis, dermis, hair follicles, sebaceous glands, scar tissue, and cancerous tissue) allowing mass spectral pathology to be performed. The cancerous regions of the tissue showed a particular increase in sphingomyelin signals that were detected in both positive and negative ion mode along with increased specific phosphatidylserine and phosphatidylinositol signals observed in negative ion mode. Samples containing mixed more and less aggressive tumor regions showed increased phosphatidylcholine lipid content in the less aggressive areas similar to a punch biopsy sample of a nonaggressive nodular lesion.
https://www.ncbi.nlm.nih.gov/pubmed/29329503
Biomarker Based Companion Diagnostics Are Enabling Precision Oncology
Accomplices of the Hypoxic Tumor Microenvironment Compromising Antitumor Immunity: Adenosine, Lactate, Acidosis, Vascular Endothelial Growth Factor, Potassium Ions, and Phosphatidylserine
Front. Immunol., 21 December 2017
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01887/full
Apoptotic Bodies Elicit Gas6-Mediated Migration of AXL-Expressing Tumor Cells
Seach for PS
https://escholarship.org/uc/item/0kn785x5
Or
https://www.google.at/url?sa=t&source=web&rct=j&url=https://cloudfront.escholarship.org/dist/prd/content/qt0kn785x5/qt0kn785x5.pdf&ved=2ahUKEwiLjcenhNPYAhUS2qQKHVXrA9gQFjAEegQIBhAB&usg=AOvVaw3cL1mMIo-CNXdeQgk6aooA
Functional Isolation of Tumor-Initiating Cells using Microfluidic-Based Migration Identifies Phosphatidylserine Decarboxylase as a Key Regulator
https://www.nature.com/articles/s41598-017-18610-5?WT.feed_name=subjects_developmental-biology
Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-Tim-3 antibodies that have functional efficacy.
Sabatos-Peyton CA1, Nevin J2, Brock A3, Venable JD3, Tan DJ2, Kassam N2, Xu F4, Taraszka J4, Wesemann L2, Pertel T2, Acharya N2, Klapholz M2, Etminan Y2, Jiang X1, Huang YH5, Blumberg RS5, Kuchroo VK2, Anderson AC2.
Author information
1Exploratory Immuno-oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, USA.Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.Department of Biotherapeutics and Biotechnology, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA, USA.Analytical Sciences, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA.Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Abstract
Both in vivo data in preclinical cancer models and in vitro data with T cells from patients with advanced cancer support a role for Tim-3 blockade in promoting effective anti-tumor immunity. Consequently, there is considerable interest in the clinical development of antibody-based therapeutics that target Tim-3 for cancer immunotherapy. A challenge to this clinical development is the fact that several ligands for Tim-3 have been identified: galectin-9, phosphatidylserine, HMGB1, and most recently, CEACAM1. These observations raise the important question of which of these multiple receptor:ligand relationships must be blocked by an anti-Tim-3 antibody in order to achieve therapeutic efficacy. Here, we have examined the properties of anti-murine and anti-human Tim-3 antibodies that have shown functional efficacy and find that all antibodies bind to Tim-3 in a manner that interferes with Tim-3 binding to both phosphatidylserine and CEACAM1. Our data have implications for the understanding of Tim-3 biology and for the screening of anti-Tim-3 antibody candidates that will have functional properties in vivo.
https://www.ncbi.nlm.nih.gov/pubmed/29308307
CD19 CAR-T therapy and sepsis: dancing with the devil
No bavi, no PS, NOTHING. SHAME
http://www.bloodjournal.org/content/131/1/7?rss=1&sso-checked=true
Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances Chemotherapy in Pancreatic Cancer
Kathleen F. Ludwig, Wenting Du, Noah B. Sorrelle, Katarzyna Wnuk-Lipinska, Mary Topalovski, Jason E. Toombs, Victoria H. Cruz, Shinichi Yabuuchi, N.V. Rajeshkumar, Anirban Maitra, James B. Lorens and Rolf A. Brekken
DOI: 10.1158/0008-5472.CAN-17-1973 Published January 2018
http://cancerres.aacrjournals.org/content/78/1/246
Maybe they" want us to pass that out of mind......
Peregrine Pharmaceuticals Announces Name Change to Avid Bioservices as Part of Transition to Dedicated Contract Development and Manufacturing Organization (CDMO) - GNW
05-Jan-2018 14:05
TUSTIN, Calif., Jan. 05, 2018 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a company working to improve patient lives by providing high quality biologics manufacturing services to biotechnology and pharmaceutical companies, today announced that it is changing its name to Avid Bioservices, Inc. as part of its transition to a dedicated contract development and manufacturing organization (CDMO). In addition to the name change, the company is also adopting the new NASDAQ ticker symbol “CDMO” (NASDAQ:CDMO). The name and ticker symbol changes will both be effective as of market open on Monday, January 8, 2018.
“As our organization transitions to a pure play CDMO, we believe it is appropriate to take advantage of the brand recognition that has been built within this highly specialized marketplace and to change the company’s name and conduct all future operations as Avid Bioservices,” said Roger Lias, Ph.D., president and chief executive officer. “Over the past 15 years, Avid has established a reputation for CDMO excellence built on biologics manufacturing expertise and a track record of consistently meeting and exceeding the needs of its clients. This level of quality is highlighted by Avid’s receipt of multiple 2017 Contract Manufacturing Leadership Awards for Quality, Reliability, Capabilities, Expertise and Compatibility. We look forward to continuing to build the Avid brand as we work to grow and diversify our CDMO business by providing our clients with the most sophisticated and highest-quality development and manufacturing services.”
Effective at market open on Monday, January 8, 2018, trading for Avid Bioservices will begin under the symbol “CDMO” (NASDAQ:CDMO). At the same time, the company’s preferred stock will begin trading under the symbol “CDMOP” (NASDAQ:CDMOP). The company’s common stock and preferred stock will continue to trade under the ticker symbols “PPHM” and “PPHMP”, respectively, until market close on Friday, January 5, 2018. The corporate name change to Avid Bioservices does not affect the rights of the company’s stockholders and no action is required by stockholders with respect to the name change. The company’s common stock has been assigned a new CUSIP number of 05368M 106 and the company’s preferred stock has been assigned a new CUSIP number of 05368M 205 in connection with the name change. Outstanding stock certificates are not affected by the name change and will not need to be exchanged.
About Avid Bioservices, Inc.
Avid Bioservices is a dedicated contract development and manufacturing organization (CDMO) focused on development and cGMP manufacturing of biopharmaceutical products derived from mammalian cell culture. The company provides a comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With nearly 25 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, Avid's services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, stability testing and 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 and product characterization. An updated corporate website featuring a new logo will be available at www.avidbio.com as of market open on Monday, January 8, 2018.
Contacts:
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. 2018
A new hope.......
A Novel Therapeutic Strategy for Cancer Using Phosphatidylserine Targeting Stearylamine-Bearing Cationic Liposomes
Manjarika De3, Sneha Ghosh3, Triparna Sen3,4, Md. Shadab5, Indranil Banerjee6, Santanu Basu, Nahid Ali'Correspondence information about the author Nahid AliEmail the author Nahid Ali
3These authors contributed equally to this work.
4Present address: Thoracic/Head & Neck Medical Oncology, Clinical Research Building, T8.3986, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
5Present address: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
6Present address: School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
Published Online: December 01, 2017
Open Access
DOI: http://dx.doi.org/10.1016/j.omtn.2017.10.019 |
http://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(17)30283-4
Novel Phosphatidylserine-Targeting Immuno-Biologicals for Cancer and Viral Treatment
https://www.flintbox.com/public/project/49886/
Contact Information
TTO Home Page: http://techfinder.rutgers.edu
Name : Shan Wan
Title : Senior Licensing Manager
Department : ORED
Email : shanwan@rutgers.edu
Phone : (848) 932-4468
Principal Investigator
Name : Sergei Kotenko, Professor
Department : Microbiology, Biochemistry and Molecular Genetics (MBMG)
Name : Viralkumar Davra, Student
Department : Microbiology, Biochemistry and Molecular Genetics (MBMG)
Name : Raymond Birge, Professor
Department : Microbiology, Biochemistry and Molecular Genetics (MBMG)
Peregrine Pharmaceuticals to Present at Biotech Showcase 2018 - GNW
02-Jan-2018 14:05
TUSTIN, Calif., Jan. 02, 2018 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a company committed to improving patient lives by manufacturing and delivering high quality biologics, today announced that its president and chief executive officer, Roger J. Lias, Ph.D., will deliver a corporate presentation at the 10th Annual Biotech Showcase™, being held January 8-10, 2018 at the Hilton San Francisco Union Square in San Francisco.
Details of this presentation are as follows:
Biotech Showcase 2018
Time/Date: 3:30 p.m. PT on Monday, January 8, 2018 Location: Hilton San Francisco Union Square Room: Yosemite – B (Ballroom Level) About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a company transitioning from an R&D focused business to a pure play contract development and manufacturing organization (CDMO). 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).
Peregrine is pursuing the licensing or sale of its proprietary R&D assets, including its lead immunotherapy candidate, bavituximab, which is currently being evaluated in clinical trials in combination with immune stimulating therapies for the treatment of various cancers. For more information, please visit www.peregrineinc.com.
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 nearly 25 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, Avid's services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, stability testing and 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 and product characterization. For more information about Avid, please visit www.avidbio.com.
Contacts:
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. 2018
Therapeutic Cancer Vaccines: How Much Closer Are We?
AuthorsAuthors and affiliations
Douglas G. McNeelEmail author
1.
Current Opinion
First Online: 28 December 2017
Abstract
The promise of immune-based therapies to treat cancer has been realized over the last several years with several breakthrough therapies, including T-cell checkpoint inhibitors and chimeric antigen receptor (CAR)-T cell therapies. While cancer vaccines have been investigated for many decades, to date only one has been approved in the USA as a treatment for existing cancer. The failure of several anti-tumor vaccines in large phase III trials has led many to question their future role in cancer treatment. Trials to date have demonstrated that many cancer vaccines can elicit tumor-specific T cells, but these T cells may be insufficient to mediate substantial anti-tumor effects without concurrent blockade of tumor-resistance mechanisms. Emerging data from preclinical models and clinical trials demonstrate that cancer vaccines have greater activity in low-volume disease and in combination with other immune-modulating therapies, including T-cell checkpoint blockade, targeting these resistance mechanisms. Because T-cell checkpoint therapies likely require the presence or activity of tumor-specific T cells, cancer vaccines may be optimal agents to use in combination to enable these therapies to work for greater numbers of patients. Future trials will explore optimal vaccine approaches and antigens that work best in combination treatment approaches and in earlier stages of disease.
https://link.springer.com/article/10.1007%2Fs40259-017-0257-y
Exosomal proteins as potential markers of tumor diagnosis
Aichun Li, Tianbao Zhang, Min Zheng, Yanning LiuEmail author and Zhi ChenEmail author
Journal of Hematology & Oncology201710:175
Published: 27 December 2017
Immunotherapy is Here to Stay: Looking Back at this Year’s Breakthroughs
December 28, 2017 Arthur N. Brodsky, Ph.D.
https://www.cancerresearch.org/blog/december-2017/immunotherapy-2017-recap-highlights
In 2018, we look forward to bringing you even more great news about advances in immunotherapy for patients. For “A Glance at the Year Ahead,” watch our upcoming webinar with Memorial Sloan Kettering’s Dr. Jedd Wolchok, director of CRI's clinical research program.
https://www.cancerresearch.org/events/webinars/immunotherapy-year-ahead-2018-jedd-wolchok
Date:January 16, 2018
Time:1:00 PM - 2:00 PM
Bavituximab drugbank
https://www.drugbank.ca/drugs/DB05136
Accomplices of the Hypoxic Tumor Microenvironment Compromising Antitumor Immunity: Adenosine, Lactate, Acidosis, Vascular Endothelial Growth Factor, Potassium Ions, and Phosphatidylserine
Front. Immunol., 21 December 2017 | https://doi.org/10.3389/fimmu.2017.01887
imagePeter Vaupel* and imageGabriele Multhoff
Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
In this minireview, we aim to highlight key factors of the tumor microenvironment, including adenosine, lactate, acidosis, vascular endothelial growth factor, phosphatidylserine, high extracellular K+ levels, and tumor hypoxia with respect to antitumor immune functions. Most solid tumors have an immature chaotic microvasculature that results in tumor hypoxia. Hypoxia is a key determinant of tumor aggressiveness and therapy resistance and hypoxia-related gene products can thwart antitumor immune responses.
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01887/full
I'M STILL A PS AND BAVI BELIEVER. IMO
Reversal of the PS-induced antitumor immunosuppression can be stimulated by PS-targeting therapeutics [e.g., Anx A5, bavituximab, see Table S1B in Supplementary Material (15)].
The Role of Tumor Microenvironment in Cancer Immunotherapy.
Frankel T1,2, Lanfranca MP1,2, Zou W3,4,5.
Author information
Ok. Thx. But why is it in a Pfizer presentation?!
HOW BIG DATA WILL DISRUPT BUSINESS
Carl Janssen, MD Country Lead Oncology Pfizer GmbH carl.janssen@pfizer.com MODELS
Nivolumab + Bavituvimab
On Page 12
https://www.google.at/url?sa=t&source=web&rct=j&url=http://www.himss.eu/sites/himsseu/files/community/community_presentations/impact17_Carl_Janssen.pdf&ved=0ahUKEwiw4KHMwqDYAhWCbVAKHbaIDuc4FBAWCBswAA&usg=AOvVaw1rnBXz5uE818LmPB2QewgX
Resolving the dark side of therapy-driven cancer cell death
Published December 20, 2017
Cancer, infection, and autoimmunity in 2018: Will we win the war?
https://www.mdlinx.com/dentistry/medical-news-article/2017/12/21/immune-system-vaccines-cancer-biomaterials-adjuvant/7498351/
5 Milestones Of 2017 In The War On Cancer
https://www.forbes.com/sites/arleneweintraub/2017/12/21/five-milestones-of-2017-in-the-war-on-cancer/#514cb56441de
JUNO THERAPEUTICS AND THERMO FISHER SCIENTIFIC ANNOUNCE CAR T MANUFACTURING PARTNERSHIP
Methods and compositions for isolating exosomes
Document Type and Number:
United States Patent 9835626
Filing Date:
02/27/2015
Publication Date:
12/05/2017
Inventors:
Schroit, Alan J. (Bellaire, TX, US)
Thorpe, Philip E. (Dallas, TX, US)
Fussey, Shelley P. M. (Houston, TX, US)
Abstract:
Disclosed are surprising new methods and compositions for isolating extracellular microvesicles such as exosomes, particularly disease-related and phosphatidylserine (PS)-positive extracellular microvesicles as exemplified by tumor- and viral-derived exosomes. The methods of the invention are rapid, efficient, cost-effective and, importantly, are suitable for use with large volumes of biological fluids and produce antigenically intact extracellular microvesicles and exosomes. The methods and compositions are based on the surprising use of acetate buffers to isolate large quantities of extracellular microvesicles, particularly tumor-derived exosomes, from solution, without damaging their morphological or functional properties or antigenicity.
http://www.freepatentsonline.com/9835626.html
Should You Get Rid of Peregrine Pharmaceuticals (PPHM) Now? - Zacks.com
18-Dec-2017 15:31:11
Dec 18, 2017
Similar to wise buying decisions, exiting certain underperformers at the right time helps maximize portfolio returns. Selling off losers can be difficult, but if both the share price and estimates are falling, it could be time to get rid of the security before more losses hit your portfolio.
One such stock that you may want to consider dropping isPeregrine Pharmaceuticals, Inc.PPHM , which has witnessed a significant price decline in the past four weeks, and it has seen negative earnings estimate revisions for the current quarter and the current year. A Zacks Rank #4 (Sell) further confirms weakness in PPHM.
A key reason for this move has been the negative trend in earnings estimate revisions. For the full year, we have seen one estimate moving down in the past 30 days, compared with no upward revisions. This trend has caused the consensus estimate to trend lower, going from a loss of 43 cents a share a month ago to its current level of a loss of 57 cents.
Also, for the current quarter, Peregrine Pharmaceuticals has seen one downward estimate revision versus no revision in the opposite direction, dragging the consensus estimate down to a loss of 14 cents a share from loss of 12 cents over the past 30 days.
The stock also has seen some pretty dismal trading lately, as the share price has dropped 12.7% in the past month.
Peregrine Pharmaceuticals Inc. Price and Consensus
Peregrine Pharmaceuticals Inc. Price and Consensus | Peregrine Pharmaceuticals Inc. Quote
So it may not be a good decision to keep this stock in your portfolio anymore, at least if you don't have a long time horizon to wait.
If you are still interested in the Medical - Biomedical and Genetics industry, you may instead consider a better-ranked stock - Emergent BioSolutions Inc. EBS . The stock currently sports a Zacks Rank #1 (Strong Buy) and may be a better selection at this time. You can seethe complete list of today's Zacks #1 Rank stocks here .
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To read this article on Zacks.com click here.
Zacks Investment Research
Copyright (c) 2017 Zacks Investment Research
Immunotherapy Shines at ASH and ESMO IO Conferences
https://www.cancerresearch.org/blog/december-2017/immunotherapy-shines-ash-esmo-conferences
Immunotherapy: A Glance at the Year Ahead
Jedd D. Wolchok, M.D., Ph.D. is the Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation; Chief, Melanoma & Immunotherapeutics Service; and Associate Director, Ludwig Center for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center. He is an Associate Director of CRI's Scientific Advisory Council.
The "Cancer Immunotherapy and You" webinar series is produced by the Cancer Research Institute and is made possible with generous support from Bristol-Myers Squibb, Genentech, Regeneron, and Advaxis.
Browse our Cancer Immunotherapy and You Webinar Series playlist on YouTube or visit the Webinars page on our website to see other webinars in this series.
Date:January 16, 2018
Time:1:00 PM - 2:00 PM
https://www.cancerresearch.org/events/webinars/immunotherapy-year-ahead-2018-jedd-wolchok
CAR-T cells and combination therapies: What's next in the immunotherapy revolution?
December 2017
Ramello MC1, Haura EB2, Abate-Daga D3.
Author information
1Dept. of Immunology, H. Lee Moffitt Cancer Center and Research Institute. Tampa, FL, United States; Dept. of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, United States; Dept. of Oncological Sciences, Morsani School of Medicine, University of South Florida, United States.
Abstract
Cancer immunotherapies are dramatically reshaping the clinical management of oncologic patients. For many of these therapies, the guidelines for administration, monitoring, and management of associated toxicities are still being established. This is especially relevant for adoptively transferred, genetically-modified T cells, which have unique pharmacokinetic properties, due to their ability to replicate and persist long-term, following a single administration. Furthermore, in the case of CAR-T cells, the use of synthetic immune receptors may impact signaling pathways involved in T cell function and survival in unexpected ways. We, herein, comment on the most salient aspects of CAR-T cell design and clinical experience in the treatment of solid tumors. In addition, we discuss different possible scenarios for combinations of CAR-T cells and other treatment modalities, with a special emphasis on kinase inhibitors, elaborating on the strategies to maximize synergism. Finally, we discuss some of the technologies that are available to explore the molecular events governing the success of these therapies. The young fields of synthetic and systems biology are likely to be major players in the advancement of CAR-T cell therapies, providing the tools and the knowledge to engineer patients' T lymphocytes into intelligent cancer-fighting micromachines.
https://www.ncbi.nlm.nih.gov/pubmed/29203440
Killing cancer softly: New approach halts tumor growth
http://www.infosurhoy.com/cocoon/saii/xhtml/en_GB/health/killing-cancer-softly-new-approach-halts-tumor-growth/
PEREGRINE PHARMACEUTICALS, INC. TO HOST EARNINGS CALLACSWIR
11/12/2017 6:38 PM
NEW YORK, NY / ACCESSWIRE / December 11, 2017 / Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM (http://pr.report/qzHomPVt) ) will be discussing their earnings results in their Q2 Earnings Call to be held on December 11, 2017 at 4:30 PM Eastern Time.
To listen to the event live or access a replay of the call - visithttps://www.investornetwork.com/company/22533 ;.
To receive updates for this company you can register by emailing info@investornetwork.comor by clicking get investment info from the company's profile.
About Investor Network
Investor Network (IN) is a financial content community, serving millions of unique investors market information, earnings, commentary and news on the what's trending. Dedicated to both the professional and the average traders, IN offers timely, trusted and relevant financial information for virtually every investor. IN is an Issuer Direct brand, to learn more or for the latest financial news and market information, visit http://www.investornetwork.com ;. Follow us on Twitter @investornetwork .
SOURCE: Investor Network
Copyright (c) 2017 Accesswire
nNRA51p0cw
© Thomson Reuters 2017. All rights reserved.
Because no PPHM-news
Resensitization of Akt Induced Docetaxel Resistance in Breast Cancer by ‘Iturin A’ a Lipopeptide Molecule from Marine Bacteria Bacillus megaterium
http://www.nature.com/articles/s41598-017-17652-z
with PS...without bavi
Merck raises stakes in lung cancer as rivals close in - RTRS
11-Dec-2017 13:00
(Repeats with no changes to text)
By Deena Beasley
LOS ANGELES, Dec 11 (Reuters) - Merck & Co Inc MRK.N, maker of the only immunotherapy approved for patients newly-diagnosed with the most common type of lung cancer, could solidify its lead by playing the long game, even as rivals edge closer.
Shares of Merck have fallen 10 percent since the drugmaker several weeks ago said it would make survival a main goal of a key lung cancer trial for immunotherapy Keytruda, extending the study by up to a year.
In the meantime, Roche Holding AG ROG.S has shaken up Wall Street expectations for the $15-billion lung cancer market, showing its Tecentriq immunotherapy slows the spread of advanced lung cancer when combined with older treatments. (Full Story) Roche Chief Executive Severin Schwan said the Swiss company has "the potential to get into the lead in first-line lung cancer."
Some Merck investors and medical experts are betting it will be worth the wait to prove that Keytruda can extend lives. Modifying the study - which previously measured cancer progression - moved completion to February 2019 from early 2018.
"Adding survival makes a lot of sense. The benefit of these drugs tend to come out over a longer period of time," said Karim Suwwan, manager of Fidelity's Select Pharmaceutical Portfolio. The fund ranked immunotherapy rivals Merck, Bristol-Myers Squibb BMY.N and AstraZeneca AZN.L in its top 10 holdings as of September 30.
Non small-cell lung cancer (NSCLC) patients in Merck's Phase 3 study are treated with Keytruda plus the chemotherapy drugs Alimta, sold by Eli Lilly & Co LLY.N, and carboplatin, or with chemo alone.
"The validity of the results will be stronger if there is a survival benefit," said Dr Roy Herbst, chief of medical oncology at Yale Cancer Center, who has been involved in several immunotherapy trials.
An earlier trial in similar patients indicated that initial treatment with Keytruda and chemotherapy improves survival, but it was too small to be definitive. Merck research chief Roger Perlmutter said making survival a primary goal of the larger study aims to confirm this outcome.
Based on the smaller study, U.S. regulators in May approved the chemo plus Keytruda combination. Keytruda alone is also approved as an initial treatment for lung cancer patients whose tumors have high levels of PDL1, a protein targeted by the drug.
In Roche's Phase III study presented last week, patients getting Tecentriq plus the older drug Avastin and chemo drugs carboplatin and paclitaxel lived for an average of 8.3 months without their disease getting worse, only modestly better than the 6.8 months seen for those getting chemotherapy and Avastin. More than a quarter of patients given the four-drug combination suffered serious side effects.
Sandra Horning, chief medical officer at Roche's Genentech unit, said survival results are expected in the first quarter of
2018.
Bristol and AstraZeneca also expect to report data from key lung cancer immunotherapy combination trials early next year.
EXTRA BENEFIT
Keytruda and Tecentriq, as well as Bristol's Opdivo and Astra's Imfinzi, are designed to unleash the body's immune system to attack cancer cells, and have been approved for a variety of cancers.
Lung cancer is the biggest oncology market, with about 220,000 people in the United States due to be diagnosed this year and 155,000 seen dying from the disease often caused by smoking.
Some industry experts expect Merck to release initial survival results as early as mid-2018. That could allow the company to expand use of the drug more quickly to patients without PDL1 in their tumors, and build a stronger case for European approval, said Tony Butler, managing director at equity research firm Guggenheim Securities.
For Tony Scherrer, co-portfolio manager at Smead Capital Management, Merck is justified in taking a slower road. Smead owns shares of Merck, but not Bristol, Roche or AstraZeneca.
"Others tried to speed up and didn't get past the FDA," he said. "Merck is doing what Merck has done over a long history - get it done right."
Shares of Merck trade at 13.6 times 2018 earnings estimates, a discount to their five-year average of 15 times, according to Thomson Reuters Datastream.
For 2023, Wall Street analysts forecast Keytruda sales of $11.6 billion, Opdivo sales of $7.7 billion and Tecentriq sales of $4.7 billion, according to Thomson Reuters data.
Drugmakers, doctors and patients have hoped that new, less toxic immunotherapies could replace chemotherapy for many cancers, but that works for only a minority of patients. So drugmakers began combining the newer therapies with chemo, other older cancer drugs and experimental treatments.
Hundreds of these trials are underway. Some have disappointed, including a cocktail of Bristol’s Opdivo with another immunotherapy, Yervoy, in lung cancers. Chemo alone tends to help only 30 percent of advanced lung cancer patients.
Researchers say that chemo could act as a catalyst, creating cellular debris that makes tumor cells more visible to the immune system.
"Nobody knows what chemo backbones could be the most powerful, and data will win out here," Daniel Chen, head of cancer immunotherapy at Roche, told investors in October.
(Reporting By Deena Beasley; Editing by Michele Gershberg and Nick Zieminski)
((deena.beasley@thomsonreuters.com; 213 955 6746; Reuters Messaging: deena.beasley.thomsonreuters.com@reuters.net))
Chemoradiation Combined with Phosphatidylserine-Targeting Antibody Enhances Systemic Anti-tumor Immune Responses
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Author links open overlay panelW.Jiang1Y.Wang2B.Freimark3L.Stepp3J.Shan3R.U.Komaki1S.H.Lin1
1
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
2
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
3
Peregrine Pharmaceuticals, Inc., Tustin, CA
Available online 23 September 2017.
Purpose/Objective(s)
Recent advances in cancer immunotherapy have sparked significant interest in harnessing the body’s immune system to fight cancer. However, the response rates of cancer immunotherapies, including immune checkpoint blockade, remain low. Strategies to enhance anti-tumor immune responses by targeting different steps along the immune activation cascade that can complement T cell-based immunotherapies are clearly needed. Here, we examine whether the addition of an antibody that targets extracellular phosphatidylserine (PS), a molecule that is recognized by myeloid derived cells, can enhance anti-tumor immune responses of chemoradiation for non-small cell lung cancer (NSCLC).
Materials/Methods
Chemoradiation (CRT) was combined with a murine monoclonal antibody (mch1N11). PS is highly expressed in both orthotopically and ectopically implanted 393P murine NSCLC models. Radiation dose was 2 Gy/day, given for 5 days. Chemotherapy consists of carboplatin and paclitaxel at a dose of 30 mg/kg and 10 mg/kg, respectively. PS-targeting antibody (mch1N11) was given at 3mg/kg for 2 weekly doses. For ectopic tumor models, bilateral tumors were established in the legs. Radiation was directed to the R leg and tumor on the L side was shielded. Tumor growth was measured either with CT imaging or digital caliper. Tumor infiltrating immune cell profiles were analyzed using immunohistochemistry. Survival analyses were performed using Kaplan-Meier method and compared using Log-rank test.
Results
CRT + mch1N11 treatment significantly inhibited growth and improved survival in mice implanted with orthotopic 393P tumors as compared to CRT alone (median: 21 vs. 15 days, HR: 2.77, P = 0.006). Tissue analyses showed that CRT significantly increased the expression of PD-L1 within the tumor and drastically reduced the number of tumor infiltrating CD8 T cells. For the CRT + mch1N11 group, a similar up-regulation of PD-L1 expression was noted. However, the addition of mch1N11 re-populated the infiltrating CD8 T cells within the tumor. In the bilateral tumor model, the addition of mch1N11 antibody to CRT resulted in tumor regression in ~40% of the non-irradiated tumors in the contralateral side as compared to 0% in the CRT alone or chemotherapy + mch1N11 groups.
Conclusion
We showed that PS-targeting combined with standard CRT can significantly prolong survival in preclinical models of NSCLC and generate enhanced systemic anti-tumor immunity against lesions outside of the irradiated field. CRT up-regulated PD-L1 expression within the tumor and depleted tumor infiltrating cytotoxic CD8 T cells. The addition of mch1N11 antibody to CRT, however, was able to re-populate this critical immune effector cell population. Together, our results demonstrate that PS-targeting antibodies may be combined with CRT to enhance intrinsic tumor immunogenicity, activate systemic anti-tumor immune responses, and act as a priming strategy to sensitize the tumor to immune checkpoint inhibition with PD-1 or PD-L1 antibodies.
Author Disclosure: W. Jiang: None. Y. Wang: None. B. Freimark: Stock; Peregrine Pharmaceuticals. L. Stepp: Stock; Peregrine Pharmaceuticals, Inc.; American Cancer Society Regional Council, Baylor University School of Nursing. J. Shan: Stock; Peregrine Pharmaceuticals, Inc.; Peregrine Pharmaceuticals. R.U. Komaki: None. S.H. Lin: Research Grant; Elekta, Inc., Hitachi Chemical, Inc., Peregrine Pharmaceuticals, Inc., Roche/Genentech, STCube Pharmaceuticals, Inc.
Copyright © 2017 Published by Elsevier Inc.
http://www.sciencedirect.com/science/article/pii/S0360301617313494