Genetic Engineering & Biotechnology News

AUG 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Genetic Engineering & Biotechnology News | | AUGUST 2017 | 29 in DNA replication and a well-known cell- proliferation biomarker. The assay offers the potential to monitor cell proliferation from a standard serum sample. Most other pro- liferation biomarkers, such as KI-67, are im- munohistological tests performed on tissue biopsies. "Proliferation biomarkers tell you how fast a tumor is growing, so they are forward- looking biomarkers," discusses Martin Shaw, business development manager, Aro- Cell. "The TK1/TK 210 protein can be used to study a wide range of malignancies and is a potentially valuable complementary di- agnostic for studying therapeutic effects and as an aid in making prognoses. Combining TK1/TK 210 with other biomarkers may lead to increased diagnostic accuracy plus better information to evaluate therapeutic responses in clinical trials." Serum TK1 enzyme activity measure- ments have been used as a cell-proliferation biomarker for close to four decades, particu- larly in hematological malignancies. How- ever, the measurement methods are complex, and require specialized equipment. Staffan Eriksson, M.D., Ph.D., professor, Swedish University of Agricultural Sciences, and an AroCell cofounder, developed TK1 specific monoclonal antibodies based on the TK 210 epitope. Studies using these antibod- ies showed that TK1 is found in serum in high molecular-weight complexes and much is enzymatically inactive, particularly in sub- jects with solid tumors. The AroCell TK 210 ELISA assay proce- dure includes a proprietary sample dilution buffer that releases TK1 protein from these complexes, enabling the quantitative measurement of serum TK1 protein levels. A standard microtiter plate ELISA, the Aro- Cell TK 210 ELISA, demonstrates similar performance characteristics to the reference TK1 enzyme activity assays in hematologi- cal malignancies but is, in most cases, much more sensitive in measuring serum TK1 from subjects with solid tumors. The CE-marked assay is currently for research use only. Visual Analytics The exploration and analysis of aggre- gated datasets is often not possible, because the biomarker discovery analytic tools are, in most cases, unavailable. Consequently, in- sufficient robust novel biomarkers are identi- fied for further validation. Once different data types associated to a translational project are aggregated, data- analysis challenges can arise. These range from the identification, as well as elimina- tion, of batch effects that can mask the real biological effects; the discovery of the corre- lations between measurements and observa- tions, such as cytokines changes and adverse events; using robust statistical methods; and the validation of the potential biomarkers. "PerkinElmer Signals for Translational addresses biomarker-discovery challenges by combining a cloud-based platform for col- laborative translational project data man- agement, with a best-in-class visual analytics environment powered by pertinent statisti- cal methods and embedded as agile TIBCO Spotfire Apps," comments Eduardo Gon- zalez, Ph.D., product manager, informatics, PerkinElmer. The Translational apps allow for the de- tection and removal of batch effects, identi- fying, ranking, and visualizing correlations in aggregated datasets with clear metrics to maximize the probability of biomarker vali- dation. Statisticians and bioinformaticians can extend the collection of apps to align with a project's specific needs. The objective is to empower scientists with embedded, well-established analytics, allowing the direct exploration and analysis of complex datasets—including omics data— to progress biomarker discovery projects. There is a strong need for domain ex- perts, like oncologists, to directly gain insight by exploring and analyzing complex transla- tional datasets in a rich visual environment. Advanced analytics for biomarker discov- ery should facilitate this self-service data exploration and analysis as well as manage streaming data from sensors in hospitals, at home, or even on wearable devices, which is arguably the next domain challenge. Translational Medicine Inflammatory biomarkers, such as secreted factors and their receptors, may be detected with RNAscope in situ hybridization assay technology provided by Advanced Cell Diagnostics. The technology, which has diverse applications (including neuroscience, stem cell, and gene- therapy applications), enabled researchers to produce this image, which highlights the RNA expression of IDO1 (green) and IFNG (red) genes in human lung cancer tissue. Insights Molecular Diagnostics The FDA approved Thermo Fisher Scientific's Oncomine™ Dx Target Test as the first next-generation sequencing (NGS)-based companion diagnostic that screens tumor samples against panels of biomarkers to identify patients who may respond to one of three dif- ferent treatments for non-small cell lung cancer (NSCLC). The Oncomine Dx Target Test exploits high-through- put, parallel-sequencing technology to screen tumor samples for 23 NSCLC genes, to identify patients who may be eligible for therapy using the Novartis drug combination Tafinlar® (dabrafenib) plus Mekinist® (trametinib) for tumors with BRAF V600E mutations, or treatment with Pfizer's Xalkori® (crizotinib) for ROS1 fusions, or therapy using AstraZeneca's Iressa® (gefitinib) for EGFR L858R mutation and Exon 19 deletions. "For people battling NSCLC, time is critical and days matter," said Joydeep Goswami, Ph.D., president of clinical NGS and oncology at Thermo Fisher, in the press release. "The Oncomine Dx Target Test rapidly guides oncologists toward the right-targeted therapy, with the goal of improving patient outcomes and the cost-efficiency of treatments." The FDA separately approved the Tafinlar plus Mekinist combination for treating patients with BRAF V600E mutated NSCLC tumors screened using the Oncomine Dx Target Test. Thermo Fisher developed the Oncomine Dx Target Test in collaboration with Novartis and Pfizer. The assay is based on Thermo Fisher's Ion AmpliSeq technology, which can screen tumor samples for multiple genetic markers using 10 nanograms of nucleic acid. FDA has in parallel granted 510(k) clearance to Thermo Fisher's Ion PGM Dx System to run the Oncomine Dx tests on for- malin-fixed paraffin-embedded (FFPE) tissue samples. Thermo Fisher is looking to expand utility of the test, which also targets 20 NSCLC-associated gene vari- ants that are currently being evaluated in clinical trials. "This first iteration of the test is just the beginning since the diagnostic claims of the Oncomine Dx Target Test may be expanded in the future based on the ex- isting panel," Dr. Goswami added. "Thermo Fisher has entered into discussions with several pharmaceutical companies looking to use the panel for FDA-approved targeted therapy applications beyond lung cancer." n FDA Clears Thermo Fisher NGS CDx for Three NSCLC Treatments

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