On April 14, 2016 Cancer Research UK reported that it has shortlisted nine teams for the final stages of its £20m Grand Challenge award* – the world’s most ambitious cancer grant helping scientists attack some of the hardest unanswered questions in cancer research (Press release, Cancer Research UK, APR 14, 2016, View Source [SID:1234510830]).

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World-class multi-disciplinary researchers representing 15 countries and 50 organisations have collaborated to make the shortlist**. The shortlisted teams are led by:

Professor Roy Bicknell from the University of Birmingham, UK, with collaborators from the USA, UK, Netherlands, Sweden and Switzerland will research developing vaccines to prevent non-viral cancers.
Professor Alan Rickinson from the University of Birmingham, UK with collaborators from the USA, Netherlands, UK, Australia, Germany, Switzerland, Japan and China will research how to eradicate EBV-induced cancers from the world.
Professor Sir Mike Stratton from the Wellcome Trust Sanger Institute, UK with collaborators from France, the USA and UK will research how unusual patterns of mutation are induced by different cancer-causing events.
Dr Jelle Wesseling from the Netherlands Cancer Institute, The Netherlands with collaborators from the USA, UK and Netherlands will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Dr Surinder Sahota from the University of Southampton, UK with collaborators from the USA, UK, Spain and Germany will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Professor Freddie Hamdy from the University of Oxford, UK with collaborators from Finland, the USA and UK will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Dr Josephine Bunch from the National Physical Laboratory, UK with collaborators from the UK will find a way of mapping tumour at the molecular and cellular level.
Professor Greg Hannon from the University of Cambridge, UK with collaborators from Switzerland, Ireland, Canada, the USA and UK will find a way of mapping tumour at the molecular and cellular level.
Professor Ehud Shapiro from the Weizmann Institute, Israel with collaborators from Israel, the UK and USA will find a way of mapping tumour at the molecular and cellular level.
Sir Harpal Kumar, Cancer Research UK’s chief executive, said: "One of the driving forces behind our Grand Challenge is the ambition to unite researchers from all sciences around the world so that they can come up with game-changing ideas to solve cancer’s most challenging questions. We’re delighted that our shortlist includes so many talented, multi-disciplinary teams.

"We’ll award at least one of these teams the first ever Grand Challenge later this year and hope that this global approach will go on to help the 14.1 million people diagnosed with cancer around the world annually."

Jim Elliott, member of the Grand Challenge patient panel, said: "When reviewing the applications for the Grand Challenge initiative I was struck by scientists’ enthusiasm to work with people they hadn’t worked with before to tackle the challenges in new ways. Some of the teams were really pioneering – spanning the globe and the sciences. I’m honoured to have been part of this innovative way to research cancer and for the opportunity to make sure that the research coming out of Grand Challenge puts patients at the heart of things."

On April 14,2016 Baxalta Incorporated (NYSE:BXLT) reported that the special meeting of stockholders to adopt the merger agreement with Shire plc (LSE:SHP, NASDAQ:SHPG) will be held on May 27, 2016, at 7:00 a.m. Central Time, for shareholders of record as of the close of business on April 11, 2016 (Press release, Baxalta, APR 14, 2016, View Source [SID:1234510829]). The special meeting will be held at Baxalta’s corporate headquarters, located at 1200 Lakeside Drive, Bannockburn, Illinois 60015.

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For more information, please refer to the merger proxy on Form S-4 that Shire has filed with the Securities and Exchange Commission (SEC).

KAHR-102 is a fusion protein that links portions of two immune and cancer-related membrane proteins; CTLA-4 and FasL (Company Pipeline, KAHR Medical, APR 14, 2016, View Source [SID:1234510828]).

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The functions of KAHR-102 in immune settings are anticipated from its component parts; The CTLA-4 component of KAHR-102 binds to B7 costimulators on antigen-presenting-cells (APC), such as dendritic cells, and thereby prevents them from engaging and triggering their cognate stimulatory CD28 receptor on T cells. The FasL component of the KAHR-102 fusion protein, binds to its cognate Fas receptor, which is upregulated on activated T cells, and thereby triggers apoptosis in these cells. The net effect of combining these blocking and triggering functions is to convert a T cell activating signal into an inhibitory one, leading to immune suppression.

KAHR-102 has also shown significant activity in cancer – both in-vitro and in cancer animal models. The CTLA-4 side of the drug targets to B7 receptors on lymphatic cancer cells, while the FasL side of the drug induces specific apoptosis of these cancer cells.

KAHR-102 forms a homo-hexamer which allows an optimal hexameric FasL structure to be specifically targeted to B7-expressing cells, such as in lymphoma cells.

On April 14, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products,reported reported the introduction of nCounter Vantage, a portfolio of assays that power 3D Biology experiments in cancer research, including immuno-oncology (Press release, NanoString Technologies, APR 14, 2016, View Source [SID:1234510827]). The nCounter Vantage portfolio provides a deeper view of cancer and immune biology by enabling multiplexed, digital analysis of DNA, RNA and protein simultaneously in a single experiment. Designed for flexibility, nCounter Vantage products can be mixed and matched, creating many new ways for cancer researchers to apply 3D Biology technology.

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"The nCounter Vantage portfolio will enable researchers to extract much more information from each patient sample to better understand a particular tumor at the genomic and proteomic level as well as its interaction with the immune system," said Dr. Jerome Galon, Research Director of INSERM. "This may lead to the identification of insightful new biomarkers and signatures that could become diagnostics with important clinical utility."

NanoString plans to unveil multiple new nCounter Vantage products at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held in New Orleans, from April 16 through April 20, 2016. These include:

For RNA, two new panels for the detection of fusion genes in lung cancer and leukemia samples
For proteins, two new panels covering solid tumor biology and immune-cell signaling
For DNA, the first of three new panels for the detection of single nucleotide variations
The company will also showcase a new version of its nSolver data analysis software, which will support 3D Biology experiments with new data merging capabilities for combining and comparing multiple panels, analyte types, and custom CodeSets in a single view.

"Because of the complexity of the immune response and tumor biology, it is likely that the next generation of biomarkers in immuno-oncology will need to integrate measurements of DNA, RNA, and protein," said Dr. Alessandra Cesano, Chief Medical Officer of NanoString Technologies. "Using Vantage assays, together with an nCounter instrument, researchers can achieve these multi-analyte measurements simultaneously on a single sample. We believe that this novel capability will pave the way for development of an exciting and more informative new category of clinical diagnostics."

New nCounter Vantage Products Featured at AACR (Free AACR Whitepaper)
The nCounter Vantage Lung Gene Fusion Panel and nCounter Vantage Leukemia Gene Fusion Panel products have been developed for Research Use Only applications, enable highly multiplexed analysis of key disease-driving gene fusions in RNA transcripts, and are commercially available now. The Lung Gene Fusion Panel includes 63 probes targeting fusions involving the ALK, ROS, RET, and NTRK1 genes. The Leukemia Gene Fusion Panel includes 42 probes targeting gene fusions and other key biomarkers expressed in ALL, AML, and CML.

Two new protein panels are initially being made available under product evaluation programs, and are expected to be commercially launched by the end of this year for use separately or in combination with other Vantage RNA and DNA panels. The first new protein panel will analyze 30 key intracellular proteins involved in immuno-oncology, and will form the nCounter Vantage RNA:Protein Immune Cell Signaling Panel when used in combination with the 770 RNA measurements included in the PanCancer Immune Profiling Panel. The second new protein panel is focused on key cancer pathways, and will form the nCounter Vantage RNA:Protein Solid Tumor Pathways Panel when used in combination with the 770 RNA measurements included in the PanCancer Pathways Panel.

In addition, the first of three new nCounter Vantage DNA panels for the detection of single nucleotide variations will be featured at the AACR (Free AACR Whitepaper) meeting. The nCounter Vantage DNA Solid Tumor Panel is designed for highly multiplexed profiling of key cancer driver mutations as well as insertions and deletions (INDELs) from as little as 5 ng of DNA. Several customers are currently involved in a product evaluation program, which will be expanded prior to commercial launch of the panel expected later this year.

At the 2016 AACR (Free AACR Whitepaper) Annual Meeting in New Orleans, Louisiana, NanoString will showcase nCounter Vantage capabilities at booth #2412.

The Hedgehog (HH) pathway has been linked to the formation of basal cell carcinoma (BCC), medulloblastoma, and other cancers. The recently approved orally active drugs vismodegib (GDC-0449) and sonidegib (LDE-225) were not only efficacious for the treatment of advanced or metastatic BCC by antagonizing the smoothened (SMO) receptor, but also produced important side effects, limiting their use for less invasive BCC. Herein, we compared a large series of SMO antagonists, including GDC-0449 and LDE-225, the clinically tested BMS-833923, CUR-61414, cyclopamine, IPI-926 (saridegib), itraconazole, LEQ-506, LY-2940680 (taladegib), PF-04449913 (glasdegib), and TAK-441 as well as preclinical candidates (PF-5274857, MRT-83) in two SMO-dependent cellular assays and for G-protein activation. We report marked differences in inhibitor potencies between compounds as well as a notable disparity between the G-protein assay and the cellular tests, suggesting that classification of drugs is assay dependent. Furthermore, we explored topical efficacies of SMO antagonists on depilated mice using Gli1 and Ptch1 mRNA quantification in skin as biomarkers of the HH signaling inhibition. This topical model rapidly discriminated drugs in terms of efficacies and potencies for inhibition of both biomarkers. SMO antagonists showed also a large variation in their blood and skin partition, suggesting that some drugs are more favorable for topical application. Overall, our data suggested that in vitro and in vivo efficacious drugs such as LEQ-506 and TAK-441 may be of interest for topical treatment of less invasive BCC with minimal side effects.

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