2017 Archived Content
A new generation of engineered predictive 3D cellular models is now emerging with the potential to transform drug screening studies for drug development, safety, and efficacy. However, achieving results with a high level of validity and reproducibility
is central in improving the acceptance of these preclinical 3D cellular models. The choice of the 3D cell model, experimental design, readouts and interpretation of data obtained from the model are critical when considering the research’s implementation
in drug discovery. Join cell biologists, tissue engineers, assay developers, screening managers and drug developers at Cambridge Healthtech Institute’s Inaugural 3D Cellular Models: Taking Screening into a New Dimension conference as
they discuss strategies that accelerate the identification of novel therapeutic leads.
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Thursday 16 November
12:00 Registration
12:15 Luncheon
Presentation: CANscript™: A Phenotypic-Based, Tumor Modeling Platform for Drug Discovery and Development
Mark Paris, Ph.D., Associate Director, Translational Applications, Mitra Biotech
We have developed and validated an ex-vivo platform technology (CANscript™) using patient material (tumor, autologous ligands and immune cells) to predict anti-tumor efficacy in the clinic across several drug classes. Data suggests this technology
can be used to understand MOA in I-O along with indication scouting, combination testing and general de-risking of cytotoxic, targeted and IO clinical programs. Supporting evidence will be presented.
13:30 Chairperson’s Opening Remarks
Catarina Brito, Ph.D., Head, Advanced Cell Models Lab, Animal Cell Technology Unit, Instituto de Biologia Experimental e Tecnológica (iBET) and Instituto de Tecnologia Química e Biológica António Xavier, Universidade
NOVA de Lisboa (ITQB NOVA)
13:35 KEYNOTE PRESENTATION: Screening Out Irrelevant Cell-Based Models of Disease
Neil Carragher, Ph.D., Professor & Principal Investigator, Drug Discovery,
Institute of Genetics and Molecular Medicine, University of Edinburgh
I describe how recent advances in cell biology are converging with state-of-the-art imaging, genomics, proteomics and informatics tools to revolutionize cell-based assay screening. We demonstrate how multiparametric high-content imaging and pathway
profiling tools combined with novel 2D and 3D assay formats advance in vitro pharmacogenomic studies across a broader variety of phenotypes, disease models and therapeutic classes.
14:05 3D Tumor Spheroids as Tools for Anticancer Therapies Screening
Ilídio J. Correia, Ph.D., Associate Professor, Faculty of Health Sciences,
Universidade da Beira Interior
The scalable and reproducible production of 3D cellular spheroids is essential for drug screening during preclinical assays. These 3D models, unlike monolayer cell culture, can provide a better model of the solid tumors found in vivo.
Spheroids spatial architecture, cellular organization, cell-cell and cell-extracellular matrix interactions, as well as drugs resistance profile is quite similar to that found in tumors.
14:35 INOVOTION’s
Unique in vivo Test is a Game-Changer for Evaluating the Efficacy and Toxicity of Anti-Cancer Treatments
Jean Viallet, Ph.D, Founder, CEO, INOVOTION
INOVOTION’s assays provide: very fast results, much lower costs, and high -sensitivity, -reliability, -predictivity. Our high-performance model allows us to grow human tumors on chicken embryos. It’s the perfect in vivo tool for anticipating preclinical mouse data and greatly reduce the level of risk in later phases.
15:05 Refreshment Break in the Exhibit Hall with Poster Viewing
15:45 Human Hepatocyte 3D Spheroids: A Breakthrough Technology for High-Throughput Drug-Drug Interaction Screening
Noushin Dianat, Ph.D., Postdoctoral Fellow, Laboratoire Colloïdes et Matériaux
Divisés, ESPCI Paris
Drug-drug interaction (DDI) through drug-metabolizing enzyme induction can lead to termination of a pre-development candidate or lead in clinical development. We have established a novel high-throughput technology to fabricate miniaturized 3D
spheroids from primary human hepatocytes for DDI screening. Hepatocyte spheroids were treated with a panel of Cytochrome P450 reference inducer compounds and DDI risk was evaluated. October 2017 Speaker Interview
16:15 A Method to Measure Kinetics of Drug Sensitivity in 3D Spheroids of Small Cell Lung Cancer Cells
Francesco Paolo Fiorentino, Ph.D., Postdoctoral
Researcher, Dipartimento di Scienze Biomediche, Università degli Studi di Sassari
Small cell lung cancer cells proliferate in vitro as 3D multi-cell floating aggregates, which make the use of SCLC cell lines difficult for drug testing. We developed a quantitative method to measure cell viability
and growth of SCLC 3D spheroids in live-cell imaging, using Corning ultra-low attachment 384 well plates and multi-mode automated microscopy with time-lapse technology (BioTek Cytation 5).
16:45 Complex Primary Cell-Based Models for Drug Discovery
Heinz Ruffner, Ph.D., Senior Investigator II, Chemical Biology and Therapeutics, Novartis Institutes
for BioMedical Research
The ultimate goal of drug discovery is the identification of efficacious and safe treatments that will address a medical need. Thus, model systems employed towards that aim should closely reflect the patho-physiology of the disease being investigated.
Organoid and organotypic cultures comprise cellular systems grown under close-to-(patho-)physiological conditions, providing a framework for proper cell function by mimicking the natural environment. Incorporation of disease-relevant insults
provide powerful and tractable models for the identification of a) molecular pathways of stem cell renewal, differentiation and apoptosis, which are central to regenerative medicine applications, and b) drug candidate leads. It is therefore
of high importance to characterize and profile such organoid cultures at the molecular level in order to develop predictive models with relevance to normal human physiology and disease. We present data describing an ex vivo model
of radiation-induced, intestinal mucositis and its potential applications for drug discovery.
17:15 Breakout Discussion Groups
This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas
and active networking.
Topic: Validating the Physiological Relevance of New 3D Models
Moderator: Neil Carragher, Ph.D., Professor & Principal Investigator, Drug
Discovery, Institute of Genetics and Molecular Medicine, University of Edinburgh
- How can we better validate the physiological- and disease-relevance on new 3D cell models?
- What role, if any, for routine transcriptomic and proteomic profiling of 2D and 3D in vitro assays with preclinical and clinical samples to compare network biology between preclinical and clinical scenarios?
- How best to reverse engineer new 3D models to ensure enhanced clinical predictivity?
- Can we retrospectively analyse and quantitatively measure the predictive value of every assay?
- Is there need for a public repository of "physiologically validated" assays with key data on predictive value?
Topic: High-Throughput Screenings in 3D Cellular Models for Cancer Research
Moderator: Francesco Paolo Fiorentino, Ph.D.,
Postdoctoral Researcher, Dipartimento di Scienze Biomediche, Università degli Studi di Sassari
- Advantages and disadvantages of 3D primary cultures, established cell lines, and co-cultures models in HTS. Which one to suggest?
- Choosing the proper 3D culture system for HTS. How to balance biological relevance and HTS limitations?
- Definition of a golden standard for data analysis and interpretation of data
- Morphology classification of spheroids. Does it really matter?
Topic: Applying 3D Models – It Takes a Village
Moderator: Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute
- What are the diverse roles of the following in engineering a viable 3D model and contributing to its acceptance in preclinical R&D?
- cell biologists
- tissue engineers
- assay developers
- screening managers
- drug developers
18:00 Dinner Short Course Registration
18:15 Close of Day
18:30 Recommended Dinner Short Course*
(SC4) Patient-Derived Organoid for Drug Development and Screening
*Separate registration required
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Friday 17 November
8:00 Registration and Morning Coffee
8:25 Chairperson’s Remarks
Carlos Ortiz de Solórzano, Ph.D., Professor and Senior Scientist, Solid Tumors and Biomarkers, Center for Applied Medical Research, University of Navarra
8:30 FEATURED PRESENTATION: Modeling Disease Microenvironment Dynamics in Bioreactors
Catarina Brito, Ph.D., Head, Advanced Cell Models Lab, Animal Cell Technology
Unit, Instituto de Biologia Experimental e Tecnológica (iBET) and Instituto de Tecnologia Química e Biológica António Xavier, Universidade NOVA de Lisboa (ITQB NOVA)
There is a need for models depicting the influence of tumor microenvironment in tumor progression and therapeutic response. We’ve developed an exogenous ECM-free cancer model system, combining bioreactor technology, cell aggregation and
microencapsulation in inert scaffolds. Co-cultures of tumor cells, fibroblasts and immune cells can be maintained in culture for months and interrogated. Recent advances employing patient-derived material will also be discussed.
9:00 Compartmentalized Microfluidic Platforms: In vitro Tool for Peripheral Tissues Innervation Studies
Meriem Lamghari, Ph.D., Researcher, Institute of Biomedical Engineering/Institute for Research and Innovation in Heath (INEB/i3S); Affiliated Professor, Instituto de Ciências Biomédicas Abel Salazar
9:30 Imaging-Based Platform for Multiplexed Analyses of Cancer Cell Spheroids, Tumor Heterogeneity and Differential Drug Response, at a Single Element Resolution
Mordechai (Motti) Deutsch, Ph.D., Director, The Biophysical Interdisciplinary Schottenstein
Center for the Research and Technology of the Cellome; Professor, Physics Department, Bar Ilan University
Novo platform, based on closely packed 2D array of optically high-quality transparent nanoliter-volume micro-chambers (MC), is presented. It contains thousands of MCs, each holding a single cell or cell aggregate without tethering. It facilitates
rapid testing of large numbers of bio-compounds for their activity in an in vivo-like environment, and detection of rare hits that may potentially become useful pharmaceuticals, all in the same device.
10:00 3D Bioprinting of iPSCs to Generate Cartilage-Like Tissue Using Chemically Modified Bio-Ink
Stina Simonsson, Ph.D., Associate Professor, Institute of Biomedicine, Department of Clinical
Chemistry and Transfusion Medicine, Sahlgrenska University Hospital
Cartilage lesions can develop into osteoarthritis (OA) and are a worldwide burden. As a prospective treatment for such lesions, we have previously shown that human-derived induced pluripotent stem cells (iPSCs) can be 3D bioprinted and directed
to form cartilage-mimics. Moreover, in a later study a new substance was used to resemble the microenvironment found in cartilage tissue. This substance was linked to nanofibrillated cellulose and mixed with alginate and iPSCs before printing.
Improved cartilage generation was achieved in the modified bio-ink.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Microengineered Airway-on-Chip to Emulate Human Lung Pathophysiology
Kambez Hajipouran Benam, Ph.D., Assistant Professor of Medicine, University of Colorado,
School of Medicine
Advances in microsystems engineering have recently made it possible to create biomimetic microfluidic cell culture devices, known as ‘organs-on-chips’, that contain continuously perfused microchannels lined by living human cells that
recapitulate the multicellular architectures, tissue-tissue interfaces, physicochemical microenvironments and vascular perfusion of the body, which potentially offer new opportunities for disease modeling and drug efficacy assessment. This
presentation discusses the microfluidic Living Human Lung Small Airway Chip technology that accurately reconstitutes normal airway physiology, mimics complex human asthmatic and COPD inflammatory processes, and permits analysis of the effects
of whole smoke, from both conventional tobacco and electronic cigarettes, delivered under physiologically relevant flow conditions that mimic breathing on the pathophysiology of differentiated human mucociliated bronchiolar epithelium cultured
in the Small Airway Chips. This talk presents data on clinical validation of these synthetic microsystems and their application for discovery of novel disease biomarkers and potential druggable targets.
11:45 Quantification of 3D Cell Migration in Microfluidics Devices
Carlos Ortiz de Solórzano, Ph.D., Professor
and Senior Scientist, Solid Tumors and Biomarkers, Center for Applied Medical Research, University of Navarra
Microfluidic devices are becoming common in preclinical studies, as they allow the study of important biological processes in physiologically relevant three-dimensional environments. I cover aspects related to the use of microfluidics in cancer
migration studies, including the design of the devices and scaffolds and the development of image processing algorithms to segment and track cells in these complex 3D environments.
12:15 Building 3D Human Tissues in vitro for Tissue- and Organ-on-Chip Applications
Giorgia Imparato, Ph.D., Senior Postdoctoral Researcher, Istituto Italiano
di Tecnologia, Center for Advanced Biomaterials for Healthcare (IIT@CRIB)
For TOC technology to meet the expectation of replacing in part the animal model, it is mandatory to proceed towards the use of tissues and organs that correctly reproduce in composition and organization the extracellular space. Indeed, while
sophisticated microdevices have been designed, the engineered tissues still remain surrogates of the native counterparts. On this basis, we established a bottom-up tissue engineering strategy to build up functional tissue in vitro.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:15 Session Break
14:15 Chairperson’s Remarks
Veronique Barban, Ph.D., Director & Virology Expert, Research and Non-Clinical Safety, Sanofi Pasteur
14:20 Human Tissue-Based Models to Improve Predictivity and Reduce Animal Use in Cancer Research
Samuel Jackson, Ph.D., Programme Manager, Efficacy, Disease Models and Safety
Pharmacology, National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)
Attrition rates in drug development have increased despite a steep rise in investment in pharmaceutical R&D, with a concomitant increase in animal use. Development of a drug can be stopped due to a failure to demonstrate efficacy in Phase
II clinical trials, which can sometimes be traced back to a failure to correctly identify efficacy in animal models. The increased use of human-derived tissue and cells carried the potential to improve the predictive nature of preclinical
testing while reducing the reliance on animal models. This presentation outlines ongoing work to harness human tissue through collaboration between clinical, research and support staff, and the NC3Rs’s role in supporting increased
development and uptake of human tissue models. By sharing examples of success and applying these to areas of unmet need in preclinical cancer modeling, the potential of using human tissue for research can be demonstrated.
14:50 3D Decellularized Human Colorectal Cancer Matrices to Tackle the Tumor Microenvironment
Maria José Oliveira, Ph.D., Assistant Researcher,
Tumour and Microenvironment Interactions Group Leader, INEB/i3S, Institute for Research and Innovation in Health, University of Porto
In the present work, we investigated the impact of human tumor matrices on macrophage polarization and cancer cell invasion. Accordingly, we developed an innovative 3D-organotypic model based on decellularized tumor tissues derived from colorectal
cancer patients' surgical resections. In contrast to normal, tumor decellularized matrices differentiated macrophages towards an anti-inflammatory phenotype, efficiently stimulating cancer cell invasion through a CCL18-dependent mechanism.
15:20 New Insights into Yellow Fever Liver Pathogenesis Based on an Organotypic Liver Tissue Model
Veronique Barban, Ph.D., Director & Virology Expert, Research and Non-Clinical Safety, Sanofi Pasteur
Yellow fever (YF) virus is responsible for mild to severe infections involving the liver, which can be prevented by vaccination with the live-attenuated strain YF17D. Transcriptome analysis of immune and metabolic responses elicited by
these viruses was conducted in a 3D liver tissue model, in time-course infection studies. The results supported a potential new mechanism whereby infection of hepatocytes by YFV 17D in vivo could
play a role in establishing local protection in the main tissue targeted by natural infection.
15:50 Close of Conference
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