AACR Annual Meeting 2015 Exhibitor Spotlight Theaters

Transcription

1 The Exhibitor Spotlight Theaters, located in the Exhibit Hall are the ideal platform for exhibiting companies to reach a specific target audience. Spotlight Theater A and Spotlight Theater B have been reserved by exhibitors to present new data, conduct promotional meetings or highlight a new service without leaving the exhibit floor. Exhibitors will be conducting one hour sessions during the exhibit hall hours to meet with attendees and discuss and array of topics. To access the theaters, please enter the Exhibit Hall through Exhibit Hall Entrance C. The theaters will be to your right, next to the Poster Section. Following is a full schedule of events. Below the schedule you ll find more details including title, abstract, and speakers for each presentation. Spotlight Theater A Sunday, April 19, :00 p.m. Bio Rad Laboratories Spotlight Theater A 2:00 p.m. Roche Diagnostics Corp. Spotlight Theater B Monday, April 20, :00 a.m. NanoString Technologies, Inc. Spotlight Theater A 10:00 a.m. Miltenyi Biotec GmbH Spotlight Theater B 12:30 p.m. RainDance Technologies Spotlight Theater A 12:30 p.m. EMD Milllipore Spotlight Theater B 3:00 p.m. 3DHISTECH Spotlight Theater A 3:00 p.m. Northwest Biotherapeutics Spotlight Theater B Tuesday, April 21, :00 a.m. Personalis, Inc. Spotlight Theater A 10:00 a.m. Illumina, Inc. Spotlight Theater B 12:30 p.m. Cellecta, Inc. Spotlight Theater A 12:30 p.m. EMD Millipore Spotlight Theater B 3:00 p.m. AstraZeneca Spotlight Theater A 3:00 p.m. BioTek Instruments, Inc. Spotlight Theater B

2 Full Schedule of Presentations, including Abstracts and Presenters Sunday, April 19, :00 p.m. Spotlight Theater A Bio Rad Laboratories Title: Precision molecular profiling of cancer using droplet digital PCR. Abstract: Droplet Digital PCR (ddpcr ) Precision Molecular Profiling of Cancer Personalized cancer care increasingly depends on detecting and monitoring mutations with extreme sensitivity and precision. Digital platforms like NGS and ddpcr are being used to identify cancer subtypes, optimize drug treatment plans, monitor residual disease, and study tumor evolution. Droplet Digital PCR permits absolute counting of target molecules, which enables precise measurement of sample input and mutational loads without amplification bias. These advantages are critical when patient samples are limiting, degradation is high, and PCR inhibitors are common such as in FFPE samples and cell free DNA (cfdna). I will summarize work covering the tracking of cell free tumor DNA during patient progression of disease and treatment monitoring, early detection of tumor cfdna in blood, detection of copy number amplifications of common genes like MYC, HER2, and EGFR, as well as the detection of KRAS mutations using a multiplex screening strategy. Speaker: Dawne Shelton 2:00 p.m. Spotlight Theater B Roche Diagnostics Corp. Title: Advances in oncology applications of NGS targeted enrichment Abstract: Targeted enrichment tools from Roche NimbleGen have helped researchers overcome challenging issues in cancer research such as tumor sample heterogeneity and detecting mutant alleles from cell free DNA. In this seminar, we will highlight significant examples of such achievements, as well as examples of detecting low frequency alleles, achieving great sequencing depth, and detecting mutations with highest sensitivity and specificity. Roche Sequencing continues to develop tools to enable innovative research in sequencing applications. We will discuss new tools for methylation and transcriptome analysis, as well as new target enrichment platforms suitable for oncology research. Speaker: Ji Wu

3 Monday, April 20, :00 a.m. Spotlight Theater A NanoString Technologies, Inc. Title: Simultaneous multi omic measurement of gene fusions, mrna and proteins at 800 plex using single molecule optical barcodes. Abstract: Both the ENCODE and TCGA projects showcased the value of quantifying multiple biomarker classes (DNA, RNA, protein) from cancer tumor samples, providing a much broader view of the underlying cancer biology. Combining multiple data types together into a single correlated analysis, however, is adversely effected by the drastically different methodologies utilized for measurement (i.e., the detection harmonization problem). For example, the fluorescence signal intensity obtained from a camera imaging a protein array (e.g., RPPA) is very difficult to correlate directly with an RNA Seq count of a clonally amplified, cdna converted, mrna molecule. New developments in multiple biomarkerclass optical barcode counting significantly reduce this problem. Recent work from the Weissleder lab [1] has shown how optical barcode technology can be utilized for multiplexed digital counting of proteins, and be combined with simultaneous digital counting of nucleic acids on a single platform. In this study we describe single molecule digital counting of mrna, proteins, and gene fusions in a single simultaneous reaction using a few thousand cells as input. Cells were fixed, permeabilized, and then profiled using: (1) PanCancer Pathway Panel (770 mrnas associated with pathways linked to key driver mutations) (2) PanCancer Immune Profiling Panel (770 mrnas associated with immune response) (3) up to 30 key cancer protein targets (+/ phosphorylation) and (4) multiple gene fusions. The current assay is configured to allow mixing and matching of different biomarker classes up to a total of 800 plex in a single reaction. All data collected in this manner are completely harmonized: within the same field ofview of the detection microscope (ncounter system) optical barcodes associated with each biomarker class are simultaneously counted, while the software keeps track of which barcodes originate from DNA, RNA, and Protein. Protein phosphorylation state changes measured by barcodes were also correlated with spatially resolved fluorescent immunohistochemistry images of the same cells. [1] Ullal et al. Science Translational Medicine 6:219 (Jan ) Speaker: Joseph M. Beechem 10:00 a.m. Spotlight Theater B Miltenyi Biotec GmbH Title: Novel and integrated tools to enable translational R&D for cellular immunotherapies Abstract: Interest in cellular immunotherapies is growing dramatically as their potential is quickly becoming realized. While offering great potential, these powerful therapeutics also bring significant new challenges in complexity of workflow required from discovery research through scaled up manufacturing. Optimization of research processes often requires months of effort as various reagents

4 and protocols are evaluated and developed to maximize yields as well as time and cost effectiveness. For those studies with the potential for clinical translation, GMP suitability and scalability should also be considered early in the process to avoid future incompatibilities and additional re development. For over 25 years, Miltenyi Biotec has been developing a variety of unique technologies which span the entire workflow of cell therapy, with solutions applicable from basic research through GMP manufacturing. Recently, Miltenyi Biotec has launched the integrated CliniMACS Prodigy system for automated production of cellular therapy products to enable efficient and cost effective clinical trials and commercialization. Examples in chimeric antigen receptor (CAR) T cell applications will be presented, demonstrating efficient integration of key steps including cell selection, activation, transduction, expansion and processing for both research as well as GMP compatible reagents and automated instrumentation. Speakers: Fred Koller, Isabelle Rivière 12:30 p.m. Spotlight Theater A RainDance Technologies Title: Detecting circulating tumor DNA by liquid biopsy and profiling solid tumors and heme based disorders with custom Next Gen DNA sequencing panels Abstract: Novel, non invasive Liquid Biopsy research applications are transforming cancer research by enabling more accurate, reliable, and early detection of circulating tumor DNA in plasma. Hear how new Next Gen DNA Sequencing technology is being deployed to rapidly detect and cost effectively analyze somatic mutations from precious liquid biopsy samples and how ultra sensitive Digital PCR technology is being applied for precise follow up mutation validation and residual disease monitoring, all from a simple blood test. Speaker: Darren R. Link 12:30 p.m. Spotlight Theater B EMD Millipore Title: Strategies for enrichment, quantitation, and characterization of microvesicles for cancer research Abstract: Due to their size and the variable nature of the biofluids in which they are typically suspended, disparate approaches to collection, isolation, and analysis of extracellular vesicles have led to efforts to enhance accuracy and correlation of data. In an effort to establish standards for workflow, sample collection, and data analysis of extracellular vesicles, the International Society for Extracellular Vesicles (ISEV) has published best practices for standardizing and reducing workflow, and eliminating contamination of EV preparations with dead cell derived vesicles. These recommendations state the absolute necessity to quantify the proportion of dead cells present in culture prior to preparing samples for enrichment and isolation of EV, necessitating the use of a cell analysis platform capable of returning quantitative data from cell health assays. Workshop participants will learn about the capabilities of a benchtop cell analyzer which couples simple, intuitive software with assays fully optimized for rapid and

5 consistent assessment of cell health parameters including count, viability, apoptotic fraction, autophagy, oxidative stress, DNA damage, and other activation of signaling pathways. Critical to understanding the precise functions of extracellular vesicles such as exosomes in tumor progression is reliable isolation of pure fractions. The current gold standard for exosome enrichment is differential ultracentrifugation, which requires specific, costly instrumentation, is lengthy, and is labor intensive. We present a rapid, ultrafiltration based approach for microvesicle isolation from biological samples, optimizing the process using an infrared spectrometer that permits simultaneous monitoring of protein quantitation and analysis of total lipid content during exosome fractionation. Finally, we will show how imaging flow cytometry improves the analysis and characterization of these microvesicles in a quantitative and reproducible manner above and beyond the current methods of analysis. Attend this interactive session to learn how to: Obtain microvesicle preparations with equivalent yield/quality to ultracentrifuge preparations Achieve better yield/quality than polymeric precipitation based techniques Quickly and consistently assess cell health prior to downstream EV workflows Detect and characterize EV directly using imaging flow cytometry Speakers: Amedeo Cappione, Haley Pugsley, Kamala Tyagarajan 3:00 p.m. Spotlight Theater A 3DHISTECH Title: Best of tissue molecular digital microscopy in cancer research Abstract: Fluorescence and brightfield digital microscopy in mesenchymal tumors research and diagnostics Recently, a large number of novel, tumor specific, pathognomonic alterations have been discovered that are relevant for mesenchymal tumor research and diagnostics. They had shed light on the involved oncogenic pathways and provided the basis of genomic sub classification of various histological entities. In case these alterations concern translocations, amplification or deletion, targeted probes can be designed and further utilized for diagnostic and research work up. For target validation, fluorescence in situ hybridization (FISH) is a commonly used technique, which can be easily adopted to routine procedures as well. Validation assays often tested on tissue microarrays (TMA) consisting of several samples from different origin. Image acquisition and manual annotation of these complex slides can be tedious and rather work intensive. With the use of automated digital image acquisition the detection of translocations or copy number alterations in individual tumor cells becomes easier permitting the analysis of multiple samples permitting quicker probe validation. Results we gained using digital microscopy on bone and soft tumors will be presented. 3D tissue reconstruction and analysis using automated multiplex immunofluorescence and whole slide imaging of serial sections: understanding of tumors structure, tumor microenvironment and effect of treatment. Accurate image acquisition is a key element in analysis of immunohistochemical (IHC) and immunofluorescent (IF) staining. Using combination of automated staining, 3DHISTECH scanners and

6 image analysis software, we optimized 3D reconstruction for IHC and IF stained serial sections. This allowed us to extend our understanding of the processes that occur in tissues not only by visualizing the structure, but also by analyzing localization and interactions of proteins within those tissues. Getting the most out of tissue microarrays: the ngtma approach for translational (and reversetranslational) research Biomarker studies in cancer research have become synonymous with tissue microarrays (TMAs). The next generation Tissue Microarray (ngtma) approach at the University of Bern combines tailored strategic planning with digital annotation on scanned slides and automated tissue microarraying to produce high quality TMAs. Precise histological zones, like tumor/stroma interfaces can be captured and transferred into ngtmas. TMA technology can also be extended to molecular applications, which may be useful for further biomarker interrogation and validation. Speakers: Karoly Szuhai, Dmitry Yarilin, Inti Zlobec 3:00 p.m. Spotlight Theater B Northwest Biotherapeutics Title: Clinical development of dendritic cell based therapies for both resectable and unresectable tumors Abstract: Dr. Bosch will discuss NW Bio s DCVax platform technology, a personalized, dendritic cell based active immunotherapy for solid tumors. Unlike conventional cancer drugs and other immune therapies, which use one active agent to hit one target on the cancer, DCVax mobilizes many active agents of the immune system to hit many targets on the cancer. NW Bio s lead product, DCVax L, is designed to treat all types of operable solid tumors. DCVax L is currently in a 348 patient international Phase III clinical trial for patients with newly diagnosed Glioblastoma multiforme brain cancer. DCVax L has also been applied in a Phase I trial with metastatic ovarian cancer, and in various other types of cancers in compassionate use cases. Dr. Bosch will provide updates on the clinical programs and related special access programs. NW Bio s second product, DCVax Direct, is designed to treat all types of inoperable solid tumors, through intra tumoral injection anywhere in the body. DCVax Direct is being evaluated in an ongoing 60 patient Phase I/II trial, in which more than 7 different cancers have been treated to date. Dr. Bosch will provide updates about this program and the technology involved. Speaker: Marnix Bosch

7 Tuesday, April 21, :00 a.m. Spotlight Theater A Personalis, Inc. Title: Solving genomic assay trade offs with an optimized, extended cancer gene panel for research and clinical applications Abstract: Choosing a genomic assay for cancer research is complicated by trade offs. Cancer gene panels are a common choice, but they target mutational hotspots in a relatively small number of genes, often for cancers that are most commonly tested and that have common genetic etiologies. A common alternative is exome sequencing, which includes all the coding genes but, due to its larger genomic footprint, cannot reach the same depths as panels and therefore is less able to deal with low tumor purity and heterogeneity. Whole genome sequencing trades off very shallow depth and coverage over vast regions of uninterpretable genomic sequence in exchange for the identification of intergenic variants and structural variant breakpoints. All of these assays can be supplemented with RNA sequencing in order to capture gene fusions, allelic expression, splice isoforms, and gene expression. RNAseq comes with its own costs: the need to extract RNA from the same tissue, the need to perform a second assay, and the need to analyze a very different type of data from DNA sequencing. The trade offs generally come down to three major issues: depth of sequencing, specific genes targeted, and cost. To solve these, we designed an extended, optimized cancer gene panel facilitating high depth sequencing at low cost. We started by identifying a comprehensive list of over 1,300 cancer genes. These genes were chosen through exhaustive cancer gene database and literature curation, and include genes from all major cancer pathways and from the Cancer Gene Census. We then took this gene list and applied an augmented targeting design strategy that we have previously used to create an augmented exome enrichment platform which fills in gaps that standard technical exomes miss. These studies demonstrate that an extended, augmented cancer gene panel strategy solves many genomic assay trade offs and leads to high accuracy and variant yield for cancer research applications. Speakers: Michael Clark, Elena Helman, Sean Boyle 10:00 a.m. Spotlight Theater B Illumina, Inc. Title: Dr. Jennifer Stone to present on Illumina's comprehensive cancer genomics portfolio Abstract: From tumor profiling to inherited risk to molecular monitoring, Illumina next generation sequencing (NGS) and microarray technologies are enabling a revolution in translational cancer research. Gain deeper insights with our expanding oncology portfolio that aid the discovery, identification, and analysis of genomic variation in cancer. Join us for a review of recent advances in Illumina sample to data solutions for cancer research and

8 some of the latest groundbreaking discoveries from the research community. Learn about solutions for whole genome, RNA and targeted sequencing which deliver high quality results from even the most challenging samples. Speaker: Jennifer Stone 12:30 p.m. Spotlight Theater A Cellecta, Inc. Title: CRISPR and RNAi platforms for genome wide loss of function genetic screens Abstract: Genome wide loss of function pooled screens provide a direct approach to identify genes regulating biological responses and find new therapeutic targets. While RNAi screens have proven effective, CRISPR/Cas9 provides an alternative screening approach. To complement our shrna screening platform, we developed pooled sgrna libraries for functional CRISPR knockout screens and compared results from sgrna and shrna library screens of PDX derived cell lines. Speaker: Paul Diehl 12:30 p.m. Spotlight Theater B EMD Millipore Title: Measuring cancer s hallmarks within tissues, serum and living cells Abstract: Given the challenges presented by tumor heterogeneity (inter patient heterogeneity, spatial heterogeneity and temporal heterogeneity), using cancer s hallmarks to fully understand disease progression requires a time resolved, multipronged, systems level approach. In this seminar, research teams present new data on some of these hallmarks: Insensitivity to antiproliferative signals, sustained angiogenesis, and tissue invasion and metastasis. The results show the utility of multiplex bead based detection systems, a vacuum driven manifold for medium throughput immunohistochemistry, a microfluidic platform for live cell analysis, and novel probes with which live cancer cells can be sorted based on RNA content prior to downstream detection of cancer s hallmarks. Seminar attendees will also be introduced to new detection reagents, including validated antibodies for site specific phosphorylation and multiplexed assays for cancer biomarkers in patient serum. Speakers: Alex Mok, Chun Yang, Wen Rong Lie

9 3:00 p.m. Spotlight Theater A AstraZeneca Title: Advanced epidermal growth factor receptor mutation positive non small cell lung cancer: understanding the drivers of resistance Abstract: Lung cancer is the second most common cancer among both men and women in the United States, and despite advances in treatment over the past several decades, mortality for lung cancer remains high. In a proportion of non small cell lung cancer (NSCLC) patients, mutations in the Epidermal Growth Factor Receptor (EGFR) gene drive tumor growth and progression, and as a result EGFR has become an important therapeutic target for these tumors. This presentation aims to educate on the molecular biology of EGFR mutation positive (EGFRm) NSCLC from diagnosis through disease progression and resistance, as well as educate on patient identification practices at diagnosis and progression. Speakers: Jeffrey Ross, Mark Socinski 3:00 p.m. Spotlight Theater B BioTek Instruments, Inc. Title: Phenotypic and mechanism of action analysis of anti metastatic molecules using 3D spheroidbased tumor invasion assays, kinetic microplate detection, and cellular microscopy Abstract: Metastasis is the main cause of death in cancer patients and one of the most complex biological processes in human diseases (Hanahan et al., 2011). The development of therapies designed to forestall the metastatic activity of tumors has been met with multiple challenges, including the choice of an appropriate cell model. Tumors in vivo exist as a three dimensional (3D) mass of multiple cell types, including cancer and stromal cells (Mao et al., 2013). Therefore, incorporating a 3D spheroid type cellular structure that includes co cultured cell types forming a tumoroid, provides a more predictive model than the use of individual cancer cells cultured on the bottom of a well in traditional twodimensional (2D) format. A second hurdle is accurate mechanism of action determination. Possessing knowledge of how invasion is interrupted provides a more complete picture before proceeding to clinical testing. A final hindrance which is necessary to overcome is the proper capture and analysis of kinetic reader based data and microscopic images during the tumor invasion process. Being able to monitor inhibitor binding, as well as tumor invasion through the matrix in a quantitative way is critical. In this presentation we will demonstrate a method for the generation of 3D spheroidal tumoroid structures, creation of a suitable invasion matrix, image based monitoring of tumor invasion, and cellular analysis of captured images. Spheroid Microplates, coated with an ultra low attachment surface, were incorporated for tumoroid formation, and performance of the invasion process. Tumor invasion tracking was performed via digital microscopy using a novel cell imaging multi mode reader. We will also demonstrate the ability to examine drug target residence time of inhibitors using a direct, homogeneous ligand binding assay prior to phenotypic invasion analysis, in addition to analysis of the involvement of

10 matrix metalloproteinases during the invasion process. The combination presents an accurate, yet easyto use method to assess target based and phenotypic effects of new, potential anti metastatic drugs. Speakers: Brad Larson