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November 2016 but never seen before:
30P - Proteomic signature analysis and application in clinical development of the
novel phosphatidylserine-targeting immunotherapy, bavituximab
D. E. Gerber (Dallas, United States of America)N. L. Kallinteris (Tustin, United States of America)
L. Horn (Nashville, United States of America)G. Losonczy (Budapest, Hungary)
R. Natale (Los Angeles, United States of America)H. Roder (Boulder, United States of America)
M. Tang (Tustin, United States of America)J. Lai (Tustin, United States of America)
J. Shan (Tustin, United States of America)R. Sanborn (Providence, United States of America)
Aim/Background
Understanding the multi-dimensional characteristics of cancer is essential to patient
selection and treatment planning. Topline results from SUNRISE, a global double-blind
Phase III trial of docetaxel + bavituximab (D+B) vs. docetaxel + placebo (D) in previously
treated non-squamous non-small cell lung cancer (NSCLC) demonstrated median overall
survival (mOS) of 10.7 months in the D+B group and 10.8 months for the D group, which
was unexpectedly different from the assumed 9.1 months mOS for D+B vs. 7.0 months
mOS used for study powering. VeriStrat , a commercially available blood-basedproteomic test for patients with advanced NSCLC was retrospectively performed on
patient samples from SUNRISE. Proteomic approaches are also being used for the
development of a potential new immunoclassifier specific for bavituximab.
Methods
Pre-treatment serum samples from all 597 SUNRISE patients were tested for protein
expression using mass spectrometry, classifying patients as VeriStrat (VS) Poor
(correlates with a more aggressive disease) or VS Good (correlates with a more favorable
prognosis). OS was analyzed by VeriStrat subgroups using Kaplan-Meier statistical
methods.
Results
VeriStrat classification was available for 569 patients. In the D+B group, 80% were VS
Good and 20% were VS Poor. In the D group 84% were VS Good and 16% were VS
Poor. Median overall survival (mOS) in all VS Good is 11.5 months (95% confidence
interval [CI], 10.6-12.9) and 5.7 (95% CI, 4.2-7.2) in all VS Poor; p?<?0.0001. Among VS
Good patients, mOS of D+B arm is 11.2 months (95% CI, 10.2-12.8) and 11.8 months
(95% CI, 10.4-13.5) in the D group; p?=?0.38. Among VS Poor patients, mOS of D+B arm
is 5.8 months (95% CI, 5.0-11.3) and 4.7 months (95% CI, 3.4-7.2) in the D group;
p?=?0.27.
Conclusions
VeriStrat results in SUNRISE are overall prognostic for OS, but not predictive for
bavituximab treatment response. The unexpected OS result in the docetaxel arm of
SUNRISE may have been impacted by the relatively high overall proportion of VeriStrat
Good patients. The development of a unique blood-based immunoclassifier for
bavituximab is underway and might be useful for patient selection in future clinical studies.
Clinical trial identification
PPHM 1202 - SUNRISE Trial NIH # - NCT01999673
Legal entity responsible for the study
Peregrine Pharmaceuticals Inc.
Funding
Peregrine Pharmaceuticals Inc.
Disclosure
D.E. Gerber: Research funding – Peregrine. N.L. Kallinteris, M. Tang, J. Lai: Peregrine
employee. L. Horn: Advisory board Genentech, Merck, Lilly, Abbvie, BI. Consulting unpaid
Xcovery, Bayer, BMS. H. Roder: Biodesix employee. J. Shan: Peregrine employee and
officer. R. Sanborn: Advisory Boards: Seattle Genetics, Peregrine Pharmaceuticals,
ARIAD. Institutional research funding: Bristol-Myers Squibb, MedImmune. Honoraria:
AstraZeneca. All other authors have declared no conflicts of interest
https://www.google.at/url?sa=t&source=web&rct=j&url=https://cslide.ctimeetingtech.com/library/esmo/browse/export/pdf/5494/18&ved=0ahUKEwjooKXL2sfUAhUCcBoKHcxGCl0QFggwMAU&usg=AFQjCNFlKfHSatonUzqkAPdj1u9_uVIbTw
Differential Binding of the HIV 1 Envelope to Phosphatidylserine Receptors
https://www.pubfacts.com/detail/28622976/Differential-Binding-of-the-HIV-1-Envelope-to-Phosphatidylserine-Receptors
A Slow “Catch and Release” Process Prolongs Immune Attack on Cancer Cells
https://reachmd.com/news/a-slow-catch-and-release-process-prolongs-immune-attack-on-cancer-cells/1510182/
Shorts seller. They buy back coming week between . 30 and .34
Pathogenic Mechanisms of how Human Parvovirus Breaks Self-tolerance
https://www.jyu.fi/science/en/personnel/Puttaraksa_Kanoktip_skaal_small.pdf
Beyond Liquid Biopsy: Blood Test Can Boost Cancer Detection, Diagnosis With the Tumor Microenvironment (TME), Early Validation Results Reveal (White Paper)
OTraces, Inc. Publishes White Paper Outlining Use of Math- and Physics-Based Techniques (Software) to Increase Biomarker and Blood Test Detection Accuracy
SYKESVILLE, MD--(Marketwired - Jun 15, 2017) - OTraces Inc. (http://ctt.marketwire.com/?release=1312640&id=11889712&type=1&url=http%3a%2f%2fwww.otraces.net%2f), a biotech company developing blood tests for cancer diagnosis, announces the development of the first blood test to access the diagnostic content of the Tumor Microenvironment (TME) -- widely recognized in cancer research as a vast and dynamic storehouse of cancer information that far exceeds the tumor itself or the known resources of DNA-based liquid biopsy (http://ctt.marketwire.com/?release=1312640&id=11889715&type=1&url=https%3a%2f%2fwww.cancer.gov%2fpublications%2fdictionaries%2fcancer-terms%3fcdrid%3d779095). OTraces researchers have issued a white paper describing its technology in detail and available at http://www.OTraces.com.
In early validation trials of prostate cancer and breast cancer patients, OTraces' TME-based cancer screening blood test appears to indicate:
Definitive determination of whether cancer is present or not;
Differentiation between aggressive and non-aggressive tumors;
Determination of cancer stage and tracking cancer progression; and
Lower Cost per test (estimated to be less than $100). "OTraces is preparing to complete prostate cancer validation trials at Johns Hopkins University Medical Center under the direction of Dr. Kenneth J. Pienta, MD
(http://ctt.marketwire.com/?release=1312640&id=11889721&type=1&url=http%3a%2f%2fwww.hopkinsmedicine.org%2fpharmacology_molecular_sciences%2ffaculty%2fbios%2fpienta.html), considered a world authority on prostate cancer research and the TME (http://ctt.marketwire.com/?release=1312640&id=11889724&type=1&url=http%3a%2f%2fcancerres.aacrjournals.org%2fcontent%2f77%2f5%2f1051.short)," said Keith Lingenfelter, OTraces' CEO. "This test could save time, money, improve patient outcomes and, most importantly, save lives."
A brief summary of the initial findings in the white paper includes:
1) Accessing the diagnostic information that resides in the "Tumor Microenvironment (TME)," the cellular structures and fluids that surround a cancer tumor and which recent research has indicated is a vast storehouse of tumor activity information that far exceeds tumor markers or the DNA isolated in circulating cancer tumor cells (CTCs) as utilized by liquid biopsy;
2) Math- and physics-based noise suppression technology that enhances diagnostic accuracy by reducing "proteomic noise" (associated with all known biomarkers, as described in the White Paper) -- a longstanding problem that continues to plague the industry and that OTraces has largely resolved as evidenced by validation trials for both prostate and breast cancer where their tests have averaged 90%+ accuracy as determined by predictive power, considered one of the most demanding performance standards in the industry. This compares favorably with an estimated current industry average of 70-75% predictive power for most tests;
3) Technology resides in cloud-based software (that is expected to amplify virtually any biomarker) which will be available via the web for in vitro cancer and disease diagnosis for physicians, laboratories and companies worldwide seeking biomarker optimization through collaboration with OTraces. Possibilities range from multiple currently marketed CLIA lab tests in the U.S. to a urine based screen for cancer in the Far East.
For more information, please visit http://www.otraces.com or email pr@OTraces.com.
About OTraces Inc.
OTraces, Inc. (http://www.otraces.com) is a privately-held biotech company based in Sykesville, MD, that provides advanced oncology diagnostic systems. It has developed a protein-based technology (proteomics) for detecting cancers with simple blood tests. OTraces is plans to raise $6 million in a preferred stock offering to complete prostate cancer validation trials in the U.S. and to advance commercialization of its breast cancer test abroad. Unlike players in the liquid biopsy field, OTraces' software is extensively patented, biomarker-agnostic, cloud-based and management believes the company's tests offer a range of clinical and cost advantages with respect to global screening criteria.
Image Available: http://www2.marketwire.com/mw/frame_mw?attachid=3148653
Investor Relations:
Keith Lingenfelter
CEO and Chairman
OTraces Inc.
+01-301-529 3824
Media Relations:
Nancy Rose Senich
Email Contact (http://www2.marketwire.com/mw/emailprcntct?id=7DB05378A585A5F7) +01-202-262-6996 cell./txt.
© 2017 Nasdaq, Inc. All rights reserved.
nMKWPRkK4a
© Thomson Reuters 2017. All rights reserved.
Immunovaccine Forms Inaugural Scientific and Clinical Advisory Committee - GNW
14-Jun-2017 13:05
HALIFAX, Nova Scotia, June 14, 2017 (GLOBE NEWSWIRE) -- Immunovaccine Inc. (TSX:IMV) (OTCQX:IMMVF), a clinical stage immuno-oncology company, today announced it has formed an inaugural Scientific and Clinical Advisory Committee (SCAC) comprised of academic and industry experts in disease areas in which Immunovaccine focuses: immuno-oncology and virology.
The Committee will provide counsel for the company’s research and development activities and access to cutting-edge ideas through collaborative data sharing and insight. Committee members will also help shape clinical programs based on real-world successes and unbiased perspectives that are founded in deep clinical research and field experience.
“We’re honored to have assembled a team of distinguished industry researchers, clinicians and collaborators to help guide strategy as we advance and expand our research and clinical programs,” said Frederic Ors, Immunovaccine’s Chief Executive Officer (https://www.imvaccine.com/about-us/leadership/#frederic-ors). “Each member brings an impressive pedigree and expertise that directly supports the disease indications we are targeting using our proprietary DepoVax™ platform. With backgrounds in virology, immunotherapy and infectious diseases, their collective experience will be invaluable as we work to bring much-needed therapies to the market for patients.”
The Scientific and Clinical Advisory Committee members include:
Barney Graham, PhD, MD
Senior Investigator, Viral Pathogenesis Laboratory, National Institute of Allergy
and Infectious Diseases Vaccine Research Center National Institutes of Health
Scott Halperin, MD
Director
Canadian Centre for Vaccinology
Ramy Ibrahim, MD
Vice President, Clinical Development Parker Institute for Cancer Immunotherapy
James Johnston, MB, BCh, FRCPC
Senior Scientist, Research Institute in Oncology and Hematology Cancer Care Manitoba
Grant McFadden, PhD
Director, Biodesign Center for Immunotherapy, Vaccines and Virotherapy Arizona State University
Michael Aaron Morse, MD
Professor of Medicine and Professor in the Department of Surgery Duke University Medical Center
Brad Nelson, PhD
Director and Distinguished Scientist, Deeley Research Centre BC Cancer Agency
Kunle Odunsi, PhD, MD, FRCOG, FACOG Cancer Center Deputy Director; Chair of the Department of Gynecologic Oncology; and Executive Director, Center for Immunotherapy Roswell Park Cancer Institute
David Spaner, PhD, MD
Senior Scientist, Biological Sciences, Odette Cancer Research Program Sunnybrook Research Institute
Pramod Srivastava, PhD, MD
Director, Center for Immunotherapy of Cancer and Infectious Diseases Eversource Energy Chair in Experimental Oncology Director of The Carole and Ray Neag Comprehensive Cancer Center University of Connecticut School of Medicine
Cancer immunitherapies
https://www.epgonline.org/uk/horizons/cancer-immunotherapies.html
Search for bavituximab
CANCER IMMUNOTHERAPY: BUILDING ON INITIAL SUCCESSES TO IMPROVE CLINICAL OUTCOMES
MKW
13/06/2017 9:00 PM
Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes
An updated discussion of approved and clinical stage agents in immuno-oncology
NEEDHAM, MA--(Marketwired - June 13, 2017) - Insight Pharma Reports, a division of Healthtech Publishing, announces the recent release of our newest cancer immunotherapy report; Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes (http://www.insightpharmareports.com/Cancer-Immunotherapy-2017-Report/).
This new report includes an updated discussion of approved and clinical stage agents in immuno-oncology, including recently-approved agents. It also addresses how researchers and companies are attempting to build on prior achievements in immuno-oncology to improve outcomes for more patients.
Highlights of this Report Include:
Approvals of checkpoint inhibitors
Biomarkers for checkpoint inhibitor treatments
Approved and clinical-stage immunotherapy biologics other than checkpoint inhibitors
Immunotherapy with TIL cells
Commercialization of TIL therapy
Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
Manufacturing issues with CAR T-cell therapies
General conclusions on the progress of cellular immunotherapy
Outlook for cancer immunotherapy For more information on these reports visit: http://www.insightpharmareports.com/Cancer-Immunotherapy-2017-Report
About Insight Pharma Reports (http://www.insightpharmareports.com) Insight Pharma Reports, a division of Healthtech Publishing, is the premier life sciences information provider offering unparalleled coverage of key issues in drug discovery and development. The reports are used by leading pharmaceutical, biotech, diagnostic, and other life science companies to keep abreast of the latest developments in pharmaceutical R&D and their potential applications and business impacts. The reports are written by experts in consulting and industry, and are supported by hundreds of hours of primary and secondary research. Insight Pharma Reports provide comprehensive coverage of salient issues in a concise, well-organized format.
About Healthtech Publishing (http://www.healthtechpublishing.com) Healthtech Publishing, a division of Cambridge Healthtech Institute, provides the life science communities with business critical intelligence through research reports and digital news, helping decision makers to gain competitive advantage and make strategic decisions. Our portfolio consists of Insight Pharma Reports' vast research reports collection and three niche digital subscription products: Bio-IT World, Clinical Informatics News and Diagnostics World.
For more information:
Daniel Miller
Insight Pharma Reports
dmiller@insightpharmareports.com
© 2017 Nasdaq, Inc. All rights reserved.
nMKWMrSYa
© Thomson Reuters 2017. All rights reserved.
Avid Bioservices to Exhibit at the 2017 BIO International Convention - MKW
13-Jun-2017 14:05
Avid Bioservices to Exhibit at the 2017 BIO International Convention Corporate Booth to Include Virtual Tour of Myford Late-Stage Clinical and Commercial Biomanufacturing Facility Featuring the Industry's Most Cutting-Edge, Single-Use Equipment and Flexible Solutions; Evening Hospitality Reception Planned for Tuesday, June 20th
TUSTIN, CA--(Marketwired - Jun 13, 2017) - 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 BIO
International Convention, being held June 19-22, 2017 in San Diego, CA. Avid
will host a corporate booth (#1411) in the conference's exhibit hall, where it
will showcase the company's comprehensive range of process development, high
quality cGMP clinical and commercial manufacturing services for the
biotechnology and biopharmaceutical industries. The company will also hold a
reception at its booth on the evening of Tuesday, June 20(th) as part of the
exhibit hall activities taking place on opening day.
At the 2017 BIO International Convention, 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. These capabilities also extend to the manufacture of biosimiliar products and are designed to support the overall ongoing growth of the company's contract development and manufacturing business.
As part of its exhibit, Avid will provide a virtual tour of the company's 40,000 square foot state-of-the-art Myford manufacturing facility, which is designated for late-stage clinical and commercial manufacturing. As previously announced, the company is on track to initially install two 2,000-liter, single-use bioreactors at the Myford facility in the near term to accommodate the growing demand for larger scale single-use bioreactors. 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 the new Myford 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 BIO International Convention, please visit: http://convention.bio.org/2017/
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, 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.
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
Email Contact (http://www2.marketwire.com/mw/emailprcntct...)
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
Email Contact (http://www2.marketwire.com/mw/emailprcntct...)
© 2017 Nasdaq, Inc. All rights reserved.
Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity
http://jci.org/articles/view/92167#ACK
First published June 12, 2017
Trovagene enters into agreement with Astrazeneca to utilize Trovera CTDNA test and services in prospective biomarker study - Reuters Investor Briefs
12-Jun-2017 14:22:35
June 12 (Reuters) - *Trovagene enters into agreement with astrazeneca to utilize trovera® ctdna test and services in prospective biomarker study *Trovagene Inc - has entered into an agreement with astrazeneca to provide trovera® urine ctdna biomarker test and services *Trovagene Inc - trovera egfr urine liquid biopsy test will initially be used in an open label prospective biomarker study
Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates.
In the past 20 years, dozensif not hundredsof monoclonal antibodies have
In the past 20 years, dozensif not hundredsof monoclonal antibodies have been developed and characterized for their capacity to mediate antineoplastic effects, either as they activate/enhance tumor-specific immune responses, either because they interrupt tumor cell-intrinsic sign transduction cascades, either because they specifically delivery poisons to malignant cells or because they prevent the tumor-stroma interaction. would investigate the protection and restorative profile of hitherto investigational mAbs in tumor individuals (resource www.clinicaltrials.gov). can be a chimeric IgG1 particular for phosphatidylserine (PS), an anionic phospholipid thatunder physiological conditionsis within the internal leaflet from the plasma membrane.99 PS translocates towards the cell surface area occasionally of cell death,100-102 cell activation and malignant transformation, and continues to be suggested to constitute a tumor vasculature-specific marker.103,104 Encouraging preclinical findings by Ran et al.99 backed the evaluation of bavituximab in clinical settings. Latest outcomes from a Stage I research indicate that bavituximab at dosages up to 3 mg/Kg/week can be well tolerated by individuals with advanced solid tumors.105 Recently (since 2011, August 1), a unitary Phase I trial continues to be launched to measure the tolerability and initial therapeutic profile of bavituximab, coupled with radiotherapy and capecitabine, in rectal adenocarcinoma individuals (“type”:”clinical-trial”,”attrs”:”text”:”NCT01634685?,”term_id”:”NCT01634685?NCT01634685) (Desk 2). Desk?2. Clinical tests recently launched to judge the restorative profile of monoclonal antibodies* is one of the group of so-called BiTEs (bispecific T-cell engagers), i.e., bi-specific mAbs that invariably focus on Compact disc3 (an element from the TCR sign transduction machinery indicated by T cells) and a tumor-associated antigen Rabbit Polyclonal to MRGX1. (in cases like this, Compact disc19, a transmembrane proteins mainly indicated by B cells).108 Hence, unlike conventional monospecific mAbs, blinatumomab exerts antineoplastic effects by bridging malignant B cells and sponsor T cells physically, advertising the cytotoxic activity of the latter hence.108 High response rates and durable remissions have already been seen in the first clinical trials testing the safety and therapeutic account of blinatumomab among B-cell NHL and B-precursor ALL individuals.109-111 Recently (since 2011, August 1), two Stage I/II trials have been initiated to investigate the safety and efficacy of blinatumomab, given as a standalone intervention, in subjects affected by B-precursor ALL (“type”:”clinical-trial”,”attrs”:”text”:”NCT01466179?,”term_id”:”NCT01466179?NCT01466179, “type”:”clinical-trial”,”attrs”:”text”:”NCT01471782?,”term_id”:”NCT01471782?NCT01471782) (Table 2). is a chimeric IgG1 specific for GD2, a disialoganglioside GD2 that is often abundant at the surface neuroendocrine tumor cells.112,113 The evaluation of the safety and efficacy of Ch14. 18 as a standalone agent for the treatment of melanoma and neuroblastoma has begun in the early 1990s,114,115 with relatively unsatisfactory results. Later on, a few clinical studies have investigated the clinical potential of combinatorial regimens consisting of Ch14.18 in association with immunostimulatory cytokines like interleukin (IL)-2 and granulocyte macrophage-colony stimulating factor (GM-CSF) or metronomic chemotherapy,116-119 reporting rather promising findings, specifically for the usage of Ch14.18 in colaboration with GM-CSF, IL-1 and isotretinoin (a retinoid) in high-risk neuroblastoma individuals.118 Recently (since 2011, August 1), two Phase I/II tests have already been launched to check the therapeutic potential of Ch14.18, alone or coupled with GM-CSF, Isotretinoin and IL-1, in neuroblastoma individuals (“type”:”clinical-trial”,”attrs”:”text”:”NCT01418495?,”term_id”:”NCT01418495?NCT01418495; “type”:”clinical-trial”,”attrs”:”text”:”NCT01592045?,”term_id”:”NCT01592045?NCT01592045) (Desk 2). (a completely human being IgG1), (a humanized IgG1) and (a completely human being IgG1) all focus on IGFR1, a transmembrane receptor that’s hyperactivated or overexpressed by most, if not absolutely all, malignant AMG706 cells, working as AMG706 an anti-apoptotic sign transducer hence. 120 Based on the results of early clinical trials, cixutumumab and dalotuzumab as single agents as well as the combination of cixutumumab and temsirolimus (an inhibitor of the intracellular signaling pathway elicited by IGFR1) are generally well tolerated by patients bearing advanced solid tumors,91,121-123 with prominent AMG706 adverse effects involving the dermis.124 Conversely, dose-limiting toxicities have been reported to develop among unselected NSCLC patients treated with cixutumumab in combination with the EGFR inhibitor erlotinib at full dosage.125 In 2012, results from 4 distinct clinical studies testing the safety and efficacy of ganitumab in patients affected by Ewing family tumors, pancreatic carcinoma or other solid malignancies have been published.126-129 Globally, ganitumabboth as a single agent and associated with targeted agents or conventional chemotherapyappears to be well tolerated and to exert antineoplastic activity, at least in a fraction of patients.126-129 This said, results from less recent Phase III studies have shown that targeting the IGF1R pathway is not associated with very clear clinical benefits in cancer patients.130 Accordingly, several anti-IGF1R programsincluding one huge randomized Phase III study that originally targeted at testing the therapeutic potential of ganitumab among prostatic cancer sufferers (“type”:”clinical-trial”,”attrs”:”text”:”NCT01231347?,”term_id”:”NCT01231347?NCT01231347)possess lately been discontinued.130,131 Recently (since 2011, August 1), two Stage II clinical studies have already been launched to check the clinical profile of cixutumumab, either being a standalone involvement or coupled with temsirolimus, in melanoma, sarcoma and human brain cancer sufferers (“type”:”clinical-trial”,”attrs”:”text”:”NCT01413191?,”term_id”:”NCT01413191?NCT01413191; “type”:”clinical-trial”,”attrs”:”text”:”NCT01614795?,”term_id”:”NCT01614795?NCT01614795). Furthermore, three Stage I/II studies have already been initiated to research the protection and efficiency of dalotuzumab, by itself.
http://dansukyoshitsu-park.com/in-the-past-20-years-dozensif-not-hundredsof-monoclonal-antibodies-have/
Don't know if we had that already:
Ludwig Presence at 2017 AACR Annual Meeting / April 2017
http://www.ludwigcancerresearch.org/news/ludwig-presence-2017-aacr-annual-meeting
Open pdf
Search for : phosphatidylserine, Wolchok or Diaz
JOHNS HOPKINS HEALTH SYSTEM - STUDY ADDS EVIDENCE THAT FLAWS IN A TUMOR'S GENETIC MENDING KIT DRIVE TREATMENT RESPONSE TO IMMUNOTHERAPY DRUGS
PUBT
08/06/2017 8:54 PM
An image of a T-cell
Credit: Photo courtesy of Robbie B. Mailliard, PhD, University of Pittsburgh Graduate School of Public Health
In an expanded, three-year clinical trial of 86 patients with colorectal and 11 other kinds of cancer that have so-called 'mismatch repair' genetic defects, scientists at Johns Hopkins Medicine and its Bloomberg~Kimmel Institute for Cancer Immunotherapy have found that half of the patients respond to an immunotherapy drug called pembrolizumab (Keytruda). In a report on the findings, which led the U.S. Food and Drug Administration to approve expanded use of pembrolizumab for patients, the researchers also say they found evidence that the immune responses closely aligned with mutations found in their cancers. The report is published online in the June 8 issue of the journal Science.
'Our study results may lead to a new standard-of-care that includes mismatch repair deficiency testing to help identify a wider group of patients who have failed other therapies but may benefit from immunotherapy drugs.' says Dung Le, M.D.
(http://www.hopkinsmedicine.org/profiles/results/directory/profile/0016139/dung-le), oncologist at the Johns Hopkins Bloomberg~Kimmel Institute, who led the clinical trial.
Mismatch repair (MMR) defects are part of a system that helps cells recognize and correct mistakes during DNA replication. For more than two decades, defective MMR genes have been linked to inherited and non-inherited (or sporadic) forms of colon cancer and used as biomarkers for diagnostic screening and chemotherapy treatment planning.
For the current Johns Hopkins study, designed and led by Le and Luis Diaz, M.D., who recently moved to the Memorial Sloan Kettering Cancer Center from Johns Hopkins, 86 adult men and women with 12 cancer types were recruited to the clinical trial at six U.S. hospitals, including The Johns Hopkins Hospital. All tested positive for mismatch repair defects and had failed to respond to at least one prior therapy. They received pembrolizumab intravenously every two weeks for up to two years. Johns Hopkins biostatistician Hao Wang, Ph.D.
(http://www.hopkinsmedicine.org/profiles/results/directory/profile/0800067/hao-wang), used a so-called 'basket design' for the clinical trial to enroll MMR-deficient patients with multiple types of cancer into a single trial.
After a median follow-up of 12.5 months, imaging scans showed that tumors shrunk by at least 30 percent in 46 of the 86 patients (53 percent). Tumors completely disappeared in 18 of the 46.
In all, 66 of 86 (77 percent) had at least some degree of disease control, including those who had partial responses, meaning their cancers shrunk by at least 30 percent in diameter, and complete responses, meaning no radiologic evidence of the tumor. This also included those whose tumors did not grow, but remained stable. At one year after the start of therapy, 65 of the 86 patients (76 percent) were alive, and 55 of the 86 (64 percent) were alive at two years.
Five of 20 patients (two with colon cancer, two with pancreatic cancer and one with small bowel cancer), who were listed as having progressive disease, initially responded to pembrolizumab, but their cancers often regrew in areas such as the brain or bone. Three were treated additionally with surgery or radiation and continued treatment with pembrolizumab. All five remained alive at the time of the data cutoff.
Twenty-one of 40 patients with colorectal cancer (52 percent) and 25 of 46 patients with cancers (54 percent) in other organs, such as pancreas, ampullary, cholangiocarcinoma, gastric, endometrial, neuroendocrine, prostate, small intestine and unknown primary responded to the drug.
The most common side effects of the immunotherapy included fatigue, skin inflammation, joint pain and thyroid dysfunction.
At the time of the data cutoff of this report, 18 patients were taken off therapy after two years of treatment. Eleven patients have been off of immunotherapy for a median of 8.3 months, and none have shown evidence of a cancer recurrence. The remaining patients had some residual disease, were taken off therapy at two years (some because of side effects) and after an average of 7.6 months, none of these patients has had evidence of disease progression.
The median point of survival without disease progression and overall survival has not yet been reached. However, the scientists estimate that disease-free survival at one and two years is 64 percent and 53 percent, respectively. Without immunotherapy, patients with advanced, treatment-refractory cancers can expect to live less than six months.
'We still do not understand why only half of the patients in the study responded and half did not,' says Drew Pardoll, M.D., Ph.D. (http://www.hopkinsmedicine.org/profiles/results/directory/profile/0800047/drew-pardoll), director of the Johns Hopkins Bloomberg~Kimmel Institute and a co-author of the report. 'But in testing for MMR deficiency, we essentially married genetic biomarkers with an immunotherapy drug to find patients we thought would be more likely to respond to this increasingly-used drug, and we believe it's a terrific example of the future of precision immunotherapy.'
He added, 'the hope is that other immunotherapy drugs can be aligned with genetic factors to further increase success.'
Pembrolizumab and other immunotherapy drugs can cost $100,000 or more per year, fueling the need to identify patients who are likely to respond to the drug. Tests for defects in mismatch repair range in cost $300 - $600.
The researchers also performed biopsies on residual tumors in 20 patients. In 12, they found no cancer cells, only inflamed cells, fibrotic tissue and mucus. These patients were more likely to survive longer without progression of their cancer (25.9 months) compared with the other eight who had residual cancer cells in their biopsies (2.9 months). However, there was no difference in overall survival between these two groups.
Using gene sequencing and methods to stimulate T-cells, immunologists, led by co-author Kellie Smith, Ph.D., of the Bloomberg~Kimmel Institute, tracked T-cells in the tumor and circulating blood that could recognize the biochemical signatures of mutations in their cancers. In three patients, they found these cells rapidly increased in the circulating blood after immunotherapy was administered, peaking at one to two months later, often prior to detecting tumor regression via CT scans.
These MMR defects were first identified in 1993 by Bert Vogelstein, M.D., (http://www.hopkinsmedicine.org/profiles/results/directory/profile/7348116/bert-vogelstein) and fellow scientists at Johns Hopkins and other institutions. The mutations disable cells' ability to repair errors in the DNA replication process, which triggers unchecked cellular growth, a hallmark of cancer.
Two decades later, an idea for the current clinical trial took root when Johns Hopkins experts discovered mismatch repair defects in a single patient with colon cancer who responded to immunotherapy while other patients with colon cancer did not.
'This was the eureka moment that led us to develop this clinical trial,' says Vogelstein, who co-directs both the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and the Genetics Program of the Bloomberg~Kimmel Institute.
To estimate how many patients with cancer may be candidates for pembrolizumab based on their mismatch repair defects, the scientists sequenced 592 genes in 12,019 patients with 32 different tumor types. They estimate that mismatch repair defects occur in nearly 5 percent of patients with 11 types of cancer, including the endometrium, stomach, small intestine, colon and rectum, cervix, prostate, bile duct, liver, neuroendocrine system, non-epithelial ovary and uterine sarcomas. This translates to approximately 40,000 (8 percent) stage I-III cancers and 20,000 (4 percent) of all stage IV cancers.
Other scientists who contributed to this research include Jennifer N. Durham, Bjarne R. Bartlett, Laveet K. Aulakh, Steve Lu, Holly Kemberling, Cara Wilt, Brandon S. Luber, Fay Wong, Nilofer S. Azad, Agnieszka A. Rucki, Dan Laheru, Ross Donehower, Atif Zaheer, Matthias Holdhoff, Christian Meyer, Shibin Zhou, Deborah Armstrong, Katherine M. Bever, Amanda N. Fader, Janis Taube, Franck Housseau, David Spetzler, Nickolas Papadopoulos, Kenneth W. Kinzler, James R. Eshleman and Robert A. Anders from Johns Hopkins; George A. Fisher of Stanford University; Todd S. Crocenzi of the Providence Cancer Center at Providence Health & Services, Portland, Oregon; James J. Lee of the University of Pittsburgh Cancer Institute; Tim F. Greten and Austin G. Duffy of the National Cancer Institute; Kristen K. Ciombor of the Ohio State University Comprehensive Cancer Center; Aleksandra D. Eyring, Bao H. Lam, Andrew Joe and S. Peter Kang of Merck; Richard M. Goldberg of the West Virginia University Cancer Institute; and Nianqing Xiao and David Spetzler of Caris Life Sciences.
Funding for this research was provided by the Swim Across America Laboratory at Johns Hopkins, the Ludwig Center for Cancer Genetics and Therapeutics, the Howard Hughes Medical Institutes, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, the 2017 Stand Up To Cancer Colon Cancer Dream Team, the Commonwealth Fund, the Banyan Gate Foundation, the Lustgarten Foundation for Pancreatic Cancer Research, the Bloomberg Foundation, the Sol Goldman Pancreatic Cancer Research Center, Merck & Co. Inc., and the National Institutes of Health's National Cancer Institute (Gastrointestinal SPORE grant P50CA062924, P30CA006973, CA163672, CA43460, CA203891, CA67941, CA16058 and CA57345).
Diaz, Le, Vogelstein, Papadopoulos and Kinzler are inventors on patents filed related to this work and Diaz, Vogelstein, Papadopoulos and Kinzler are a founder of PapGene and Personal Genome Diagnostics (PGDx). Diaz is a consultant for Merck, Illumina, PGDx and Cell Design Labs. PGDx and PapGene, as well as other companies, have licensed technologies from Johns Hopkins University, on which Diaz, Vogelstein, Papadopoulos and Kinzler are inventors. Some of these licenses and relationships are associated with equity or royalty payments. The terms of these arrangements are being managed by Johns Hopkins in accordance with its conflict of interest policies.
Johns Hopkins Health System published this content on 08 June 2017 and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on 08 June 2017 18:54:53 UTC.
Original document
http://www.hopkinsmedicine.org/news/media/releases/study_adds_evidence_that_flaws_in_a_tumors_genetic_mending_kit_drive_treatment_response_to_immunotherapy_drugs
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Hitachi and MD Anderson to collaborate in research for treatment of oropharyngeal cancer of the head and neck
http://www.publicnow.com/view/FFCFC3B45E2195DB3DB8CE7C2611BB1114C390ED?2017-06-07-15:01:32+01:00-xxx9770
New Class of Double-Duty Magnetic Nanoparticles Engineered to Lower Cancer’s Defenses While Firing up Immune System
http://www.publicnow.com/view/4A6BFCD4C2F0232DD00E8F8292C2EBD3984E74CF?2017-06-07-14:01:36+01:00-xxx37
Acknowledgments
We thank the Integrated Genomics and Bioinformatics core facilities at MSKCC for RNA sequencing and genome alignments, respectively; Romina Goldszmid, Jedd Wolchok, Taha Merghoub, Jackie Bromberg, Mark Connors, and Marianita Santiana for sharing critical reagents; Tamas Balla, Howard Young, and Anton Zilman for helpful discussions; Robin Winkler-Pickett for assuring a smooth lab move to the NIH; Ron Germain for critically reading the manuscript; and all members of the G.A.-B. lab. J.O.-Y. is grateful to Carlos Carmona-Fontaine for microscopy help and insightful discussion. This work was supported by the U.S.-Israel Binational Science Foundation (# 2012327 to G.A.-B. and O.K.), by the US National Institutes of Health ( R01-AI083408 to G.A.-B.), by the Intramural Research programs of the NHLBI, NIH (N.A.-B.), and by the Center for Cancer Research, NCI, NIH (G.A.-B.).
http://www.cell.com/molecular-cell/fulltext/S1097-2765(17)30328-3
yes, that all SOUNDS very good - BUT
.....when can we SMELL it?
Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation
http://www.cell.com/molecular-cell/fulltext/S1097-2765(17)30328-3
1 June 2017
Another disapoointed Day After. What comes next?
Novartis announces ground-breaking collaboration with IBM Watson Health on outcomes-based care in advanced breast cancer
https://www.novartis.com/news/media-releases/novartis-announces-ground-breaking-collaboration-ibm-watson-health-outcomes
Means nothing - just a Reuters Quote.
PEREGRINE PHARMA REPORTS SIGNIFICANT IMPROVEMENT IN LUNG CANCER CASES TREATED WITH BAVITUXIMAB - SHARES UP 7% PPHM.O
MIDTRD
05/06/2017 2:40 PM
08:39 AM EDT, 06/05/2017 (MT Newswires) -- Peregrine Pharmaceuticals (PPHM) shares were up almost 7% pre-market Monday after the company reported 'significant improvement' in certain lung-cancer patients treated with its drug bavituximab, in a phase 3 trial of patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer.
Peregrine said results demonstrate that patients in the study's bavituximab treatment arm who met certain conditions had a statistically significant improvement in median overall survival as compared to patients in the same treatment arm, also with certain conditions.
The company said the test results 'inform our clinical development strategy going forward and provide additional rationale for combining bavituximab with checkpoint inhibitors.'
Price: 0.64, Change: +0.04, Percent Change: +6.63
Copyright (c) 2017 MT Newswires, a Division of MidnightTrader, Inc. All rights reserved.
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PEREGRINE PHARMACEUTICALS INC - ?RESULTS SUPPORT HYPOTHESIS THAT BAVITUXIMAB MAY DEMONSTRATE GREATER EFFECT IN "COLD" TUMORS EXPRESSING LOW TO NO PD-L1?
RTRS
05/06/2017 2:06 PM
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ASCO17: Day 1 Immunotherapy Highlights
June 03, 2017
https://www.cancerresearch.org/blog/june/asco17-day-1-immunotherapy-highlightsAny news?
Lung Cancer:
In a 3-D system using patient-derived non-small cell lung carcinoma (NSCLC) cells, the combination of bavituximab (anti-phosphatidylserine antibody) and nivolumab (anti-PD-1 checkpoint inhibitor) led to enhanced immune responses compared to either immunotherapy alone. (Scott J. Antonia, M.D., Ph.D., was involved in this work.)http://abstracts.asco.org/199/AbstView_199_193973.htmlIn a 3-D system using patient-derived non-small cell lung carcinoma (NSCLC) cells, both nivolumab and pembrolizumab (anti-PD-1 checkpoint immunotherapies) individually promoted anti-tumor macrophage activity and T cell activation. (Scott J. Antonia, M.D., Ph.D., was involved in this work.)http://abstracts.asco.org/199/AbstView_199_193442.htmlIn patients with metastatic non-small cell lung carcinoma (NSCLC) who were treated with anti-PD-1/PD-L1 checkpoint immunotherapy, those who responded were much more likely to exhibit early proliferation of PD-1+ killer T cells in their peripheral blood compared to non-responders. (Rafi Ahmed, Ph.D., who sponsors CRI postdoctoral fellow William H. Hudson, Ph.D., was involved in this work.)http://abstracts.asco.org/199/AbstView_199_193150.html
Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression
Pls delete if already known.....
Published June 2017
http://mcr.aacrjournals.org/content/15/6/753
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh N. Nguyen, Anita Antes, Allen Krantz,Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V. Kotenko and Raymond B. Birge
P3.02c-051 A Pre-Treatment Serum Test Based on Complement and IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel
Article · January 2017
https://www.researchgate.net/publication/312265717_P302c-051_A_Pre-Treatment_Serum_Test_Based_on_Complement_and_IL-10_Pathways_Identifies_Patients_Benefiting_from_the_Addition_of_Bavituximab_to_Docetaxel
Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy.
https://www.ncbi.nlm.nih.gov/pubmed/28467800
Don't know if this is realy from June 2017 or it's old....or what ever.....
Immunotherapy: Questions Persist Despite Successes
—Dosing, biomarkers, cost among unresolved issues
Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation
With: Phosphatidylserine and Bavituximab (REFERENCES)
http://www.cell.com/molecular-cell/pdf/S1097-2765(17)30328-3.pdf?bcsi_scan_1014b4c4c7c5e188=340nuzFMukbXXywagFYiaCx8SzBCAAAAuLvFTg==&bcsi_scan_filename=S1097-2765(17)30328-3.pdf
From yesterday!
JOHNS HOPKINS HEALTH SYSTEM - TIP SHEET: IMMUNOTHERAPY TRIAL RESULTS FOR CANCER AMONG RESEARCH PRESENTATIONS BY JOHNS HOPKINS SCIENTISTS
PUBT
01/06/2017 6:53 PM
Cancer cells
Credit: iStock
NOVEL IMMUNE DRUG COMBO CONTROLS MELANOMA IN PATIENTS PREVIOUSLY-TREATED WITH STANDARD THERAPY
Combining two checkpoint inhibitors, drugs that remove inhibitory signals and restore the immune system's ability to fight cancer, may be effective in shrinking melanoma tumors or preventing their growth in some patients who previously received standard therapy, according to new research results from the Johns Hopkins Bloomberg~Kimmel Institute. (ASCO Abstract 9520).
Although currently-available immune checkpoint inhibitors have improved survival for some patients with melanoma or other types of cancer, Johns Hopkins study leader Evan J. Lipson, M.D. (http://www.hopkinsmedicine.org/profiles/results/directory/profile/2194148/evan-lipson), notes that these therapies are often ineffective. For example, in two recent studies, nivolumab (Opdivo), which targets an immune-inhibiting protein known as PD-1, led to two-year survival in only about 60 percent of patients with advanced melanoma.
In an effort to increase that percentage, Lipson and his colleagues tested whether adding a second, still experimental checkpoint inhibitor, which targets another immune-inhibiting protein known as LAG-3, could be effective in treating patients with advanced melanoma.
Lipson and his collaborators in the U.S. and Europe administered nivolumab and the anti-LAG-3 checkpoint inhibitor every two weeks to patients whose melanomas had progressed during or after previous treatment with at least one immune checkpoint therapy. Among 48 patients, 6 (13 percent) experienced a reduction in tumor size, while tumors from an additional 20 patients (42 percent) stabilized. Median duration of follow-up was 14 weeks.
These results, Lipson says, suggest that some patients for whom standard therapy is ineffective may benefit from this novel combination of immune checkpoint inhibitors, which remove molecular 'brakes,' allowing the immune system to launch a more effective anticancer attack.
He adds that ongoing clinical trials at Johns Hopkins and elsewhere are currently testing this drug combination in patients with other types of cancer, or adding a third checkpoint inhibitor to the mix.
'Anti-LAG-3 has demonstrated its importance as a component of combination immune checkpoint inhibitor therapy. We continue to develop these novel regimens in order to safely and effectively unleash the tremendous power of the human immune system for as many cancer patients as possible,' Lipson says.
CANCER IMMUNOTHERAPY BEFORE - NOT AFTER - SURGERY COULD BE MORE EFFECTIVE
* Pre-op delivery of checkpoint inhibitor dramatically shrinks
tumors in nearly half of lung cancer patients in small clinical trial
In a small clinical trial, nearly half of 21 patients with lung cancer
pre-operatively given a drug that helps the immune system attack cancer
responded so dramatically their tumors nearly or completely disappeared, Johns
Hopkins scientists report. The findings, (ASCO Abstract 8508), suggest that
the timing of immunotherapy may be critical to successful cancer treatment in
people whose lung tumors are operable.
Administering standard chemotherapy before surgery, known as neoadjuvant therapy, has a long history in treating cancer, explains study leader Patrick Forde, M.B.B.Ch.
(http://www.hopkinsmedicine.org/profiles/results/directory/profile/0554010/patrick-forde), assistant professor at the Johns Hopkins Bloomberg~Kimmel Institute. However, only about 20 percent of patients with non-small cell lung cancer, the most common type of this disease, seem to benefit from it.
Checkpoint inhibitors, drugs that remove inhibitory signals and restore the immune system's cancer-fighting capability, have been approved to treat several cancers, including lung cancer, since 2014.
To test whether patients would do better if the immunotherapy were given before surgery, Forde and his colleagues at Johns Hopkins and Memorial Sloan Kettering Cancer Center gave two doses of the checkpoint inhibitor nivolumab (Opdivo) to 21 patients with non-small cell lung cancer over the four weeks leading up to their scheduled tumor removal surgeries.
Results showed that in nine patients, tumors had regressed more than 90 percent at the time of surgery. After surgery to remove residual tumors, further investigation showed that most patients' tumors had an infiltration of immune cells, suggesting that the drug had prompted an aggressive immune attack against these cancers. An average of nine months after surgery, 17 (81 percent) of the 21 patients remained alive and recurrence-free.
Forde and his colleagues plan to study giving nivolumab in combination with other checkpoint inhibitors before surgery, and to test a longer pre-operative course of nivolumab. 'It might be a matter of timing,' he says. 'The immune system might need longer in some patients to fight off cancer cells.'
TESTOSTERONE-LOWERING THERAPY MIGHT SPUR IMMUNE SYSTEM TO FIGHT PROSTATE CANCER
A drug frequently prescribed to men with prostate cancer to lower levels of testosterone that fuel cancer growth might also stimulate an immune attack on prostate tumors, a new study led by Johns Hopkins researchers shows. (ASCO Abstract 5077.) The findings, researchers say, could lead to new strategies for fighting prostate cancer, the second most common cancer in American men.
In 2005, experiments at Johns Hopkins in the laboratory of Charles Drake, M.D., Ph.D., showed that reducing testosterone in mouse models of prostate cancer prompts cancer-fighting immune cells known as CD8+ T cells to enter the prostate gland. This effect was even more pronounced when these animals also received a prostate cancer-specific vaccine, called GVAX, that encourages an immune response against this disease.
To test the concept in people, Emmanuel Antonarakis, M.D. (http://www.hopkinsmedicine.org/profiles/results/directory/profile/9451649/emmanuel-antonarakis), associate professor of oncology and urology at the Johns Hopkins University School of Medicine and a member of the Kimmel Cancer Center, Drake, now at NewYork-Presbyterian/Columbia University Medical Center and Angelo DeMarzo, M.D., Ph.D.
(http://www.hopkinsmedicine.org/profiles/results/directory/profile/0007730/angelo-demarzo), of Johns Hopkins, studied 48 prostate cancer patients in a presurgical clinical trial.
All participants had localized prostate cancer and were scheduled for surgery to remove their prostate glands. Four weeks before the surgeries, 13 men received GVAX along with cyclophosphamide, a standard chemotherapy drug that lowers the number of immune cells, called Tregs, which are known to inhibit immune responses. Two weeks later, these men received degerelix, a hormone drug that lowers testosterone levels, and then had their prostate glands removed two weeks later. A separate group of 15 patients received degarelix by itself, two weeks before surgery.
The remaining group of 20 men in the control group received no pre-surgical treatment prior to undergoing surgery to remove their prostate glands.
After each prostatectomy, the researchers examined the surgically removed tissue to determine whether the immunotherapy and hormone treatments had an immune-stimulating effect. They found that the CD8+ T-cell density was more than twice as high in prostate tissue from men who received any treatment before surgery compared with those who didn't. However, the group that received both GVAX and cyclophosphamide in addition to degerelix had comparable CD8+ T-cell densities to those who received degerelix alone.
'What that tells us is that the most important factor in stimulating prostatic CD8+ T-cells wasn't GVAX or cyclophosphamide but the degerelix itself,' Antonarakis says.
On the down side, the immune-stimulating effect wasn't isolated to CD8+ T cells; the levels of Tregs also rose as well in both treatment groups, Antonarakis adds, which could dampen the CD8+ T-cells' cancer-fighting effects. To address this issue, Antonarakis says, ongoing clinical trials at Johns Hopkins are testing the use of a combination of degerelix with either prostate cryotherapy, which applies freezing temperatures to tumors and releases immune-stimulating molecules from the prostate into the bloodstream; or with immunotherapy drugs known as checkpoint inhibitors such as pembrolizumab.
HEAD AND NECK CANCERS 'SATURATED' WITH MUTATIONS AND AN IMMUNE-SYSTEM GENE SIGNATURE MAY RESPOND BETTER TO IMMUNOTHERAPY
In a look-back study of patients with head and neck cancers enrolled in a clinical trial of the immunotherapy drug pembrolizumab (Keytruda), Johns Hopkins physicians have found preliminary evidence that cancers with abundant mutations and a gene signature specific for immune system T-cell inflammation may respond better to immunotherapy drugs that block a protein called PD-1.
Pembrolizumab is FDA-approved for five cancer types, including head and neck cancer, and approximately 18 percent of patients with the disease respond to the drug, Johns Hopkins researchers say. However, physicians currently have no way to tell which patients with advanced cancers may respond.
Ranee Mehra, M.D.
(http://www.hopkinsmedicine.org/profiles/results/directory/profile/10003645/ranee-mehra), associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, and her colleagues analyzed tumor tissue samples from 107 patients with head and neck cancer who received pembrolizumab. (ASCO Abstract 6009). Using genomic sequencing, the researchers looked at the abundance of mutations in the patients' cancers and the expression of genes related to T-cell inflammation. The researchers also determined whether patients were positive or negative for human papillomavirus (HPV), which is linked to head and neck cancer. An increased mutation burden can produce large amounts of abnormal, foreign-looking proteins and is thought to make the malignant cells more visible to the immune system and susceptible to immunotherapy.
Of the 107 patients, 21 responded to pembrolizumab and 14 of them were negative for HPV. Among 39 patients in the total group who had high mutation burden in their cancers, 12 (31 percent) responded to the drug. Some 52 of the 107 had increased expression of T-cell inflammation genes, and 14 of them (27 percent) responded to pembrolizumab. Of 30 who had both high mutation burden and high T-cell inflammation gene expression, 12 responded (40 percent).
Mehra says that the small number of responders is a limitation of the study, but she says there seems to be a trend in better response to pembrolizumab among those with high mutation burden and T-cell inflammation gene expression.
'Our study suggests tumor genetic biomarkers that need further evaluation in future clinical trials of immunotherapy,' says Mehra. 'Patients who respond to these drugs tend to respond for a long time, so it's important to predict who may be more likely to respond.'
Johns Hopkins Health System published this content on 01 June 2017 and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on 01 June 2017 16:53:32 UTC.
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Sorry for that Info!
THE PD-1 / PD-L1 COMBINATION THERAPIES REVOLUTION: NEW EP VANTAGE REPORT SEES IMMUNO-ONCOLOGY TRIALS TRIPLE AND KEYTRUDA STEAL THE CROWN FROM OPDIVO
BSW
01/06/2017 3:55 PM
The PD-1 / PD-L1 Combination Therapies Revolution:
New EP Vantage Report Sees Immuno-oncology Trials Triple and Keytruda Steal the Crown from Opdivo
The battle to find a cure for cancer has led to an explosion in the number of clinical trials using anti-PD-1 and anti-PD-L1 antibodies combined with other therapeutic approaches, says a new report by EP Vantage, the wholly independent editorial arm of Evaluate, the trusted provider of life science commercial intelligence.
When EP Vantage published its first PD-1/PD-L1 combination report in November 2015 there were 215 studies, as of April 2017 there were 765. The latest PD-1/PD-L1 report, released today, also reveals that Keytruda has overtaken Opdivo as the combination partner of choice.
Other key findings include
There are now 268 combo trials involving Keytruda and 242 with Opdivo, of which 86 combine Opdivo with Yervoy. Keytruda’s dominance comes as the drug continues to impress in clinical trials
The number of studies combining PD-1/PD-L1s with chemotherapy have surged, potentially spurred by Roche’s efforts with Tecentriq
IO-IO combos also represent a significant part of the analysis. Keytruda, Opdivo and Tecentriq are in 56, 54 and 32 IO-IO combo studies respectively
The most popular indication for combinations is lung cancer, which makes up the biggest single market (16%), followed by melanoma and sarcoma (13%), which has so far showed the best efficacy for PD-1/PD-L1s. But uro-gynecological (12%) and haematological cancers are becoming more prevalent
There is little to suggest a slowdown in this field, given the speed with which immuno-oncology combination studies have proliferated and the blockbuster potential of the anti-PD-1/PD-L1 class.
Combination trials may also be driven by a desire to improve on the striking efficacy of the first wave of anti-PD-1/PD-L1 agents, but also by a need to improve on the limited efficacy seen with many novel oncology projects.
“It will be interesting to watch whether combinations with small molecules and other therapeutic agents will win out in the end,” said report author Jacob Plieth.
“However, the focus will increasingly turn from throwing everything into a combination and seeing what sticks to generating real data. Sprinkling magic immuno-oncology dust will not come to the rescue of mediocre assets,” added Mr Plieth. “Ultimately, it will all come down to hard data.”
About Evaluate
Evaluate is the trusted provider of commercial intelligence including product sales and consensus forecasts to 2022 for commercial teams and their advisors within the global life science industry. We help our clients make high value decisions through superior quality, timely, must-have data and insights, combined with personalised, expert client support. Our online subscription services cover the pharmaceutical, biotech and medtech sectors. Our Custom Services group delivers project based analytical and data services. EP Vantage, our independent, award-winning editorial team, offers data-driven, forward-looking news, commentary and analysis on a daily basis.
Copyright Business Wire 2017
Parker Institute for Cancer Immunotherapy Scientists to Present Research at ASCO 2017 on IDO Pathway Inhibitors, Novel CAR-Ts and the Microbiome's Potential in Immunotherapy - PRN
01-Jun-2017 15:01
SAN FRANCISCO, June 1, 2017
SAN FRANCISCO, June 1, 2017 /PRNewswire-USNewswire/ -- Investigators affiliated with the Parker Institute for Cancer Immunotherapy will present results on some of the most noteworthy developments in immuno-oncology research at the 53(rd) Annual Meeting of the American Society of Clinical Oncology (ASCO). The event takes place at the McCormick Convention Center in Chicago from June 2 through June 6.
ASCO is the largest cancer conference in the United States. The event is expected to draw more than 30,000 scientists, clinicians, advocates and others to discuss advances in the field. Parker Institute scientists will present data on promising new checkpoint therapy agents, immunotherapy resistance, T-cells engineered to combat cancer and how the microbiome may play a role in survival and response to cancer immunotherapy treatment.
SELECT ABSTRACTS
IDO-1 inhibitor combined with nivolumab shows promise for solid tumors: Preliminary phase I/II results of ECHO-204 (http://abstracts.asco.org/199/AbstView_199_184081.html)
The authors will present new trial data on epacadostat, an inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) immunosuppressive enzyme that helps control anti-tumor immune response. This drug was tested in combination with nivolumab for head and neck, melanoma, ovarian and colorectal cancers. Adil Daud, M.D., Parker Institute member researcher at the University of California, San Francisco (UCSF), is a co-author. (Abstract 3003)
CRISPR knockouts used to test resistance to PD-1 checkpoint inhibitors (http://abstracts.asco.org/199/AbstView_199_194123.html)
Investigators used CRISPR/Cas9 gene editing technology to generate cell JAK1, JAK2 and beta-2-microglobulin (B2M) knockout cells. Cells lacking functionality in these genes were resistant to anti-PD-1 checkpoint blockade, likely due to different mechanisms, as explored in this study. Antoni Ribas, M.D., Ph.D., Parker Institute center director at the University of California, Los Angeles (UCLA), is principal investigator. (Abstract 3077)
Adenosine A2a receptor (A2aR) antagonist shows promise in patients with solid tumors resistant to PD-1 and PD-L1 checkpoint agents (http://abstracts.asco.org/199/AbstView_199_186068.html)
A novel drug, CPI-444, shows promise for renal cell carcinoma and non-small cell lung cancer patients resistant to checkpoint agents targeting PD-1 and PD-L1. The drug showed anti-tumor activity alone and combined with atezolizumab. Parker Institute center co-director Lawrence Fong, M.D., of UCSF, is first author. Matthew Hellman, M.D., Ph.D., a Parker Institute member researcher at Memorial Sloan Kettering Cancer Center, is a co-author. (Abstract 3004)
Diversity and composition of the gut microbiome associated with response and survival in metastatic melanoma patients on anti-PD-1 therapy (http://abstracts.asco.org/199/AbstView_199_193510.html)
A greater diversity in gut flora and an abundance of a specific bacteria was associated with improved survival among patients on anti-PD-1 checkpoint therapy. Jennifer Wargo, M.D., Parker Institute member researcher at the University of Texas MD Anderson Cancer Center, is principal investigator. (Abstract 3008)
The Parker Institute is collaborating with Dr. Wargo on developing clinical trials to test whether influencing the microbiome makeup can affect patient response to checkpoint blockade treatments.
Liver metastases in melanoma patients linked to lower PD-1 blockade response (http://abstracts.asco.org/199/AbstView_199_191526.html)
Jeffrey Bluestone, Ph.D., CEO and president of the Parker Institute, and Adil Daud, M.D., a Parker Institute member researcher at UCSF and head of the university's melanoma clinical research program, report that melanoma patients with liver metastases do not respond as well to anti-PD-1 immunotherapy agents, suggesting that where cancer metastasizes plays a role in a patient's responsiveness to immunotherapy treatment. This study also looks at the potential mechanism behind those findings in mice and humans. (Abstract 3072)
Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab) + tremelimumab in patients with advanced solid tumors (http://abstracts.asco.org/199/AbstView_199_191149.html)
The combination therapy of durvalumab and tremelimumab showed a manageable safety profile and preliminary evidence of clinical activity when used on solid tumors in this phase I multi-center study. The principal investigator is Jedd Wolchok, M.D., Ph.D., the Parker Institute center director at Memorial Sloan Kettering Cancer Center, where first author Margaret Callahan, M.D., Ph.D., is also a Parker Institute member researcher. (Abstract 3069) AWARDS, LECTURES AND SESSIONS OF NOTE
Driving New CARs for Cancer: PACE CARS, NASCARs, and SWEET CARs June 3, 11:15 a.m.
Location: Hall B1
Carl H. June, M.D., Parker Institute center director at the University of Pennsylvania, is the recipient of the 2017 David A. Karnofsky Memorial Award and Lecture for his outstanding contributions to the field. His talk will focus on new developments in CAR-T therapy, which he pioneered. He will be awarded as part of the opening session.
Oral Abstracts: Developmental Therapeutics—Immunotherapy June 5, 2017, 1:15 - 4:15 p.m.
Location: Hall D1
Padmanee Sharma, M.D., Ph.D., Parker Institute center co-director at The University of Texas MD Anderson Cancer Center, co-chairs this session that features leading edge research on novel immunotherapy drugs. Several Parker Institute affiliated researchers will be part of the presentations and discussion panels, including Crystal Mackall, M.D., Parker Institute center director at Stanford Medicine, and Antoni Ribas, M.D., Ph.D., Parker Institute center director at UCLA.
Novel Approaches to Immunotherapy in Solid Tumors June 2, 2017, 1 p.m.
Location: S100a
James Allison, PhD, Parker Institute center director at The University of Texas MD Anderson Cancer Center, will present from 1 to 1:45 p.m. during the session, "On the Shoulders of Giants: Historical Approaches to Immunotherapy in Solid Tumors."
About the Parker Institute for Cancer Immunotherapy The Parker Institute for Cancer Immunotherapy 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.
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/parker-institute-for-cancer-im...
SOURCE Parker Institute for Cancer Immunotherapy
Shirley Dang, Science Communications Manager, Parker Institute for Cancer Immunotherapy, sdang@parkerici.org, 415-930-4385
LOL !!!!!
Functional organization of the HIV lipid envelope
28 September 2016!!!
But with: Bavituximab and PS
If that is known - pls.......
https://www.nature.com/articles/srep34190
Novartis CEO sees no need for big takeover - Reuters News
31-May-2017 17:44:54
• Novartis CEO says no need for "big deal"
• Company could unload assets worth $50 bln
• Expects Trump proposals on drug prices in 3 months
Recasts to focus on M&A
By John Miller
ZURICH, May 31 (Reuters) - Novartis NOVN.S does not need a big acquisition to kick-start growth, Chief Executive Joe Jimenez told investors on Wednesday, playing down suggestions he could use proceeds from a slew of asset sales for a significant takeover.
The Swiss drugmaker is reviewing potential disposals of its struggling eyecare business Alcon, its consumer drugs joint venture with GlaxoSmithKline GSK.L and a stake in rival Roche ROG.S that could raise a combined $50 billion. (Full Story)
Amid speculation Novartis might use proceeds to buy AstraZeneca AZN.L or Bristol-Myers Squibb BMY.N to fill holes in its cancer drug portfolio, Jimenez said he remained focused on smaller purchases of up to $5 billion to bolster his pipeline.
"Obviously, there's been a lot of speculation because that would be a lot of capital," Jimenez said at an event at Novartis's research campus in Boston.
"We don't need a big deal," he said. "Our strategy in M&A is to do bolt-on acquisitions."
Money-losing Alcon, which makes surgical equipment for cataracts as well as contact lenses and solutions, is undergoing a strategic review, with "all options" on the table. (Full Story)
Jimenez promised an update by year's end on the division, which Novartis assigns a remaining book value of $21 billion.
While Jimenez still expects his Sandoz generic drug division's 2017 revenue to be "broadly in line" with last year's numbers, he warned price pressure in the United States had intensified in the second quarter.
Sandoz, whose $10.1 billion in revenue in 2016 made up a fifth of Novartis's total, is among generics makers including India's Sun Pharmaceutical Industries SUN.NS and Lupin LUPN.NS that have said U.S. revenue growth will be muted this year. (Full Story)
TRUMP CARD
Jimenez, who as chairman-elect of U.S. drugmaker industry lobby group PhRMA met President Donald Trump earlier this year, told investors he expected the administration to come forward with proposals on curbing U.S. drug prices "within the next three months". (Full Story)
Trump in January said drug companies were "getting away with murder" with high drug prices. (Full Story)
Still, Jimenez said on Wednesday he was optimistic the Republican president would strike an industry-friendly balance, possibly incorporating "outcome-based pricing" models that reward drugmakers whose products save the healthcare system money. (Full Story)
"We're watching it very closely, we're heavily involved," Jimenez said of PhRMA's efforts in Washington.
(Editing by Michael Shields and Mark Potter)