Cambridge Healthtech Institute’s Inaugural
Applying 3D Models
Bridging the Gap Between 2D Cell Culture and Animal Models
JUNE 19-20, 2019
Finding physiological relevant models for complex and heterogeneous diseases has never been more important. Cells grown in a monolayer are useful to explore diseases but lack tissue-level structure that is key to mimicking the human body. Animal models
have fundamental species differences that decrease their predictive abilities. Join us at Cambridge Healthtech Institute’s Inaugural Applying 3D Models conference as leaders in the field discuss the use of spheroids, tumoroids,
organoids, organs-on-a-chip and other microfluidic strategies for drug discovery across several therapeutic areas.
Final Agenda
Wednesday, June 19
12:00 pm Registration Open
12:00 Bridging Luncheon: Structural Maturation in the Development of hiPSC-Cardiomyocyte Models for Pre-clinical Safety, Efficacy, and Discovery
Nicholas Geissse, PhD, CSO, NanoSurface Biomedical
Alec S.T. Smith, PhD, Acting Instructor, Bioengineering, University of Washington
hiPSC-CM maturation is sensitive to structural cues from the extracellular matrix (ECM). Failure to reproduce these signals in vitro can hamper experimental reproducibility and fidelity. Engineering approaches that address this gap typically trade off
complexity with throughput, making them difficult to deploy in the modern drug development paradigm. The NanoSurface Car(ina)™ platform leverages ECM engineering approaches that are fully compatible with industry-standard instrumentation including
HCI- and MEA-based assays, thereby improving their predictive power.
12:30 Transition to Plenary
12:50 PLENARY KEYNOTE SESSION
2:20 Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing
2:25 Meet the Plenary Keynotes
3:05 Chairperson’s Remarks
Jason Ekert, PhD, MBA, Head, Complex In Vitro Models, R&D Platform Technology & Science, GlaxoSmithKline
3:10 KEYNOTE PRESENTATION: Implementation of Multi-Dimensional Cellular Tumor Models with Increased Translational Relevance in Preclinical Oncology Drug Development
Jason Ekert, PhD, MBA, Head, Complex In Vitro Models, R&D Platform Technology & Science, GlaxoSmithKline
The current preclinical oncology drug discovery paradigm involves lengthy and costly optimization/lead discovery campaigns, often using cellular or in vivo tumor models with weak translational relevance that don’t
closely resemble human solid tumors. I will highlight opportunities/challenges in implementing 3D solid tumor models. I will outline key components that should be considered when developing, validating, scaling and automating 3D solid tumor models
that are more physiologically relevant.
3:40 Translational Models to Profile Oncolytic Viruses in Glioblastoma Multiforme
Aaron Goldman, PhD , Director, Drug Resistance Group, Brigham and Women's Hospital, Faculty and Instructor in Medicine, Harvard Medical School, Breast Cancer Alliance Early Career Investigator, Harvard-MIT Health Sciences and Technology
Overlapping, translational models may have the potential to more rapidly advance rational deployment of OV in the clinic. Here, we discuss the complementary use of in-vitro and human ex-vivo models to profile the
translational potential of a re-engineered herpes simplex virus (HSV-1) in glioblastoma multiforme. The ex vivo human tumor model we deploy preserves the native 3-dimensional structure of the tumor and contains patient-autologous
peripheral blood mononucleated cells to capture immune response when exposed to OV.
4:10 Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer
Hervé Tiriac, PhD, Associate Project Scientist, Department of Surgery, UC San Diego
New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for pancreatic cancer patients. Combined genomic, transcriptomic, and therapeutic profiling of patient-derived organoids can identify molecular
and functional subtypes of pancreatic cancer, predict therapeutic responses and facilitate precision medicine for pancreatic cancer patients.
4:40 Organoid Systems for Industry-Relevant Assay Endpoints
Michael Hiatt, Senior Scientist, Bioengineering, Research and Development, STEMCELL Technologies
5:10 4th of July Celebration in the Exhibit Hall with Poster Viewing
5:30-5:45 Speed Networking: Oncology
6:05 Close of Day
5:45 Dinner Short Course Registration
6:15 Dinner Short Course*
*Separate registration required.
Thursday, June 20
7:15 am Registration Open
7:15 Breakout Discussion Groups with
Continental Breakfast
8:10 Chairperson’s Remarks
Louis Scampavia, PhD, Senior Scientific Director of HTS Chemistry and Technologies, Scripps Research
8:15 Ex Vivo Profiling of Response to PD-1 Blockade Using Organotypic Tumor Spheroids
Elena Ivanova, PhD, Senior Scientist, Medical Oncology, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute
We have developed an approach enabling ex vivo studies of anti-PD-1/PD-L1 and combination therapies using murine- and patient derived organotypic tumor spheroids (mDOTS/pDOTS) cultured in a novel 3D microfluidic system.
We have demonstrated that the DOTS platform is feasible for image analysis, cytokine profiling, and RNA expression studies including single-cell RNAseq. This combination of techniques allows us to characterize dynamic, high-resolution profiles of
checkpoint blockade response.
8:45 TANK-Binding Kinase 1 (TBK1) as a Cancer Immunotherapy Target
Russell W. Jenkins, MD, PhD, Assistant Professor, Department of Medicine, Center for Cancer Research, Massachusetts General Hospital
Innate resistance to PD-1 blockade remains a major challenge and strategies to overcome immune suppression and render the TME more permissive to T cell infiltration and function are under pre-clinical and clinical evaluation. TANK-binding kinase 1 (TBK1)
is emerging as an attractive, novel cancer immunotherapy target to enhance response to anti-PD-1 therapies. Here, we describe tumor-intrinsic and tumor-extrinsic roles of TBK1 in modulating response to PD-1 blockade.
9:15 Microfluidic Assembly Of Hydrogel-Based Immunogenic Tumor Spheroids For Evaluation Of Anticancer Therapies And Biomarker Release
Tania (Tali) Konry, PhD, Assistant Professor, Department of Pharmaceutical Sciences, Northeastern University
This study describes the development of an integrated droplet microfluidics-based platform for high-throughput generation of immunogenic DLBCL spheroids. The spheroids consist of three cell types (cancer, fibroblast and lymphocytes) in a novel hydrogel
combination of alginate and puramatrix, which promoted cell adhesion and aggregation. This system facilitates dynamic analysis of cellular interaction, proliferation and therapeutic efficacy via spatiotemporal monitoring and secretome profiling.
9:45 Translational Immuno-Oncology: Use of Human Tissue Ex-Vivo Model in Preclinical Research
Yuan Zhang, PhD, Vice President, Pharmalegacy
We have developed a fresh human tumor tissue culture model that remains phenotypically intact in the tumor microenvironment to fill the gap between clinical and experimental models. Here, we used this model to assess the activities of anti-cancer immunomodulatory
therapies, and discuss the potential of using this model to perform mini-trials to predict result of clinical trials as an invaluable and cost-effective preclinical platform.
10:15 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Poster Winner Announced
11:00 A PDX/Organoid Biobank of Advanced Prostate Cancer for Disease Modeling and Therapeutic Screening
Kathleen Kelly, PhD, Lab Chief, Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute
Organoid cultures provide a technology to culture epithelial cancers that otherwise do not propagate in vitro. We have established a preclinical platform of PDX- and patient biopsy-derived metastatic castrate resistant
prostate cancer (mCRPC) organoids that is experimentally facile for high throughput and mechanistic analysis. The genetic and phenotypic variability and stability of models, genetic manipulations, and the utility of such a platform for drug sensitivity
determination will be discussed.
11:30 Enabling High Throughput Screening with Patient Derived 3D Cancer Spheroids/Organoids
Louis
Scampavia, PhD, Senior Scientific Director, Molecular Medicine Department, Scripps Research, Florida Campus
3D enabling technologies are now cost-effective and practical for generating cancer spheroids/organoids by combining the use of cell-repellent surfaces and magnetic bio-printing. The Scripps Research High Throughput Screening (HTS) center has adapted
these breakthroughs for spheroid-based drug screening using patient-derived cancer cell lines in a 1536w format. Large-scale drug testing and reformulation/repurposing studies as well as novel drug discovery campaigns are now implemented using
HTS automation in a cost-effective manner.
12:00 pm Cancer Models: Immune Checkpoint Blockade Therapies and Metastatic Disease
Roger D. Kamm, PhD, Green Distinguished Professor of Mechanical and Biological Engineering, Departments of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology
Microfluidic technologies for 3D culture have enabled more realistic models of cancer, both as disease models, and as platforms for drug screening or patient-targeted therapies. Two applications will be discussed. First, we explore the mechanisms
by which circulating tumor cells home to the brain, transmigrate across the vascular endothelium, and initiate a metastatic tumor. Next, we demonstrate how microfluidics can be used to screen for effective patient-specific immunotherapies.
12:30 Enjoy Lunch on Your Own
1:35 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing
1:45-2:00 Speed Networking: Last Chance to Meet Potential Partners and Collaborators!
2:20 Chairperson’s Remarks
Piotr Walczak, MD, PhD, Associate Professor, Radiology, Johns Hopkins University
2:25 A Perfused Human Blood–Brain Barrier On-A-Chip for High- Throughput Assessment of Barrier Function and Antibody Transport
Nienke Wevers, Scientist/PhD Candidate, Mimetas
We present a novel model of the human blood-brain barrier (BBB) in a high-throughput microfluidic system that allows parallel culture of 40 models at once. The model comprises brain endothelial cells, astrocytes, and pericytes and shows formation
of a functional barrier. Passage of an antibody targeting the human transferrin receptor was markedly higher than penetration of a control antibody, indicating that this model could support further discovery and engineering of antibody BBB-shuttle
technologies.
2:55 In Vitro and In Vivo Models to Evaluate P-gp and BCRP Activity in Regulating BBB Penetration
Guangqing Xiao, PhD, Associate Director, DMPK, Takeda
The presentation will give an overview of expression of Pgp and BCRP in BBB and BCSFB, species difference in expression, how Pgp and BCRP regulate BBB penetration, in vitro models to identify Pgp and BCRP substrates,
and preclinical in vivo models to assess brain penetration, and how to use in vitro and in vivo models to identify compounds with good brain
penetration.
3:25 Exploring the Utility of iPSC-Derived 3D Cortical Spheroids in the Detection of CNS Toxicity
Qin Wang, PhD, Scientist, Drug Safety Research and Evaluation, Takeda
Drug-induced Central Nervous System (CNS) toxicity is a common safety attrition for project failure during discovery and development phases due low concordance rates between animal models and human, absence of clear biomarkers, and a lack of predictive
assays. To address the challenge, we validated a high throughput human iPSC-derived 3D microBrain model with a diverse set of pharmaceuticals. We measured drug-induced changes in neuronal viability and Ca channel function. MicroBrain exposure
and analyses were rooted in therapeutic exposure to predict clinical drug-induced seizures and/or neurodegeneration. We found that this high throughput model has very low false positive rate in the prediction of drug-induced neurotoxicity.
3:55 Linking Liver-on-a-Chip and Blood-Brain-Barrier-on-a-Chip for Toxicity Assessment
Sophie Lelievre, DVM, PhD, LLM, Professor, Cancer Pharmacology, Purdue University College of Veterinary Medicine
One of the challenges to reproduce the function of tissues in vitro is the maintenance of differentiation. Essential aspects necessary for such endeavor involve good mechanical and chemical mimicry of the
microenvironment. I will present examples of the management of the cellular microenvironment for liver and blood-brain-barrier tissue chips and discuss how on-a-chip devices maybe linked for the integrated study of the toxicity of drugs
and other molecules.
4:25 Close of Conference