Screening and Functional Analysis of 3D Models

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Tuesday, November 1

11:00 am Conference Registration

12:45 pm Dessert Break in the Exhibit Hall with Poster Viewing

3D Models for Oncology Drug Screening

1:30 Chairperson’s Opening Remarks

Bonnie Sloane, Ph.D., Distinguished Professor, Pharmacology, Wayne State University

1:35 Image-Based Quantification of Tumor Heterogeneity and Treatment Response in Microfluidic and Heterocellular 3D Models for Ovarian Cancer

Imran Rizvi, Ph.D., Assistant Professor, Dermatology, Harvard Medical School, and Assistant in Biomedical Engineering, Wellman Center for Photomedicine, Massachusetts General Hospital

Targeting the molecular and microenvironmental determinants of tumor heterogeneity is critical to overcoming treatment resistance. Development of bioengineered models and image analysis tools to design mechanistically informed combinations that overcome heterogeneity from physical stress and stromal partners in ovarian cancer is described. Priming hetero-cellular 3D ovarian cancer nodules with photodynamic therapy (PDT), a clinically approved, light-based biophysical modality, significantly improves response to chemotherapy and decreases heterogeneity in complex 3D tumor models.

2:00 Application of Heterogeneity Analysis in Cellular Models and Tissues in the Context of Quantitative Systems Pharmacology

Albert Gough, Ph.D., Associate Professor, Drug Discovery Institute, University of Pittsburgh

Quantitative Systems Pharmacology uses data from patient samples to develop and validate cell models for applications in discovery. Both types of data exhibit heterogeneity, and it is essential to understand the spatial and population components of heterogeneity. In this presentation, I will discuss the application of pairwise mutual information to the quantitation of spatial heterogeneity and the application of heterogeneity indices to the quantitation of population heterogeneity in cell models.

2:25 Organoids, a Disease and Patient Specific in vitro Model System

Robert Vries, Ph.D., Managing Director, Hubrecht Organoid Technology Foundation

2:55 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Pathomimetic Cancer Avatars for Screening and Functional Analyses

Bonnie Sloane, Ph.D., Distinguished Professor, Pharmacology, Wayne State University

Our laboratories have pioneered novel techniques for functional live-cell imaging of protease activity in pathomimetic avatars that model both cellular and non-cellular aspects of tumors and their microenvironment. These pathomimetic avatars allow us to test interventions that impact directly or indirectly on proteolytic pathways. To facilitate their use for screening of therapeutic approaches, we have fabricated culture chambers that support long-term growth and live-cell imaging. We predict that pathomimetic avatars grown in our engineered chambers will accelerate identification of druggable pathways, screening of drug and natural product libraries and the entry of validated drugs or natural products into clinical trials.

4:10 Quantitative Signatures of Cancer Cell Shape and Phenotypic Heterogeneity in 4D

Chris Bakal, Ph.D., Team Leader, Dynamical Cell Systems, The Institute of Cancer Research

Here I will discuss how the evolution of our quantitative profiling methods, developed originally in 2D systems, now allows us to perform high-throughput screens for regulators of cancer cell shape in 3D and 4D. In particular, I will discuss the identification of genes encoding components of signaling networks that couple mechanical and geometrical aspects of the extracellular matrix (ECM) to changes in cell shape, and how dysregulation of these networks leads to increased phenotypic heterogeneity that is characteristic of aggressive tumor populations. Finally, I will discuss how we validate our findings in vivo using novel integrative analysis.

4:35 Choosing and Designing 3D Cell Culture Models for High-Throughput Screening of Nutrients, Raw Materials and Drugs

Sophie A. Lelièvre, DVM, Ph.D., LLMPH, Professor, Basic Medical Sciences, Scientific Director, 3D Cell Culture Core (3D3C) Facility, Purdue University Discovery Park

Each cell culture model ought to be tailored to the scientific query. I will give examples of important phases in the design of 3D cell culture models, and address differences between classical 3D culture systems and organs-on-a-chip for the purpose of high-throughput screening. Discussion points will also emphasize the importance of the cell culture medium and of the readouts for the mimcry of in vivo tissue structure and function.

5:45 ThinkTank Registration

6:00-9:00 Dinner Expert ThinkTank
(SC2): How to Meet the Need for Physiologically Relevant Assays

Separate registration required

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Wednesday, November 2

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

Patient-Derived Tumor Models for Screening and Functional Analysis

8:00 Chairperson’s Remarks

Geoffrey A. Bartholomeusz, Ph.D., Associate Professor/Director, Target Identification and Validation Program, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center

8:05 Clinical Relevance of Patient-Derived 3D Tumor Microenvironments via Quantitative Multi-Spectral Imaging Approaches

Edna Cukierman, Ph.D., Associate Professor, Cancer Biology Program, Fox Chase Cancer Center

The role of desmoplasia in cancers (e.g., pancreatic) remains unclear. Our desmoplastic 3D model uses cells harvested from surgical samples and allows dissecting between desmoplastic fibroblast-derived extracellular matrices and matrix-induced cellular responses. In vitro findings are validated using the original surgical samples in an integrative approach combining multi-colored immunofluorescence and a new quantitative algorithm. This process is then applied to human tissue cohorts granting clinical relevance to our mechanistic findings.

8:30 Patient-Derived 3D Neurospheres for Glioblastoma Drug Screening

Darren Finlay, Ph.D., Research Assistant Professor and Director of Tumor Analysis, Sanford Burnham Prebys Medical Discovery Institute

3D spheroid tumor culture models more accurately represent the environment of cancers in situ. Furthermore, patient-derived cultures that have never been exposed to fetal bovine serum are actually representative of patients’ cancers whereas commonly used cell lines rarely are. Here we show isolation and characterizations of patient-derived glioblastoma “stem-like” cells, and demonstrate their utility as 3D neurospheres for drug screening and patient sub-stratification.

8:55 Use of ex vivo Models Generated from PDX Tumors as a Platform for Anti-Cancer Drug Discovery

Geoffrey A. Bartholomeusz, Ph.D., Associate Professor/Director, Target Identification and Validation Program, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center

Patient-derived xenograft (PDX) systems, an important component in the personalized approach for cancer therapy, are however, costly and time consuming. We have developed an ex vivo tumor tissue system closely replicating the original PDX tumor, and preliminary data suggests its potential to serve as a platform to identify new therapies for solid tumors. We predict our ex vivo system will significantly reduce both the cost and turnaround time associated with PDX systems.

9:20 A Hyaluronic Acid-Based Hydrogel System for 3D High Throughput Drug Screening

Pamela E. Constantinou, Ph.D., Assistant Research Professor, Department of BioSciences, Rice University

Using a hyaluronic acid (HA)-based hydrogel system, we have coupled high-throughput robotic delivery with automated advanced imaging, to provide a highly reproducible system for drug screens on spheroid cultures of prostate and endometrial cancer cell lines and, more recently, PDX models.

9:45 High-Content Profiling of Primary Patient-Derived 3D Tumor Models for Response Prediction and Tailored Cancer Therapy

Christoph Sachse, Ph.D., Site Head Berlin, NMI TT Pharmaservices

We will present two complementary approaches: (1) in a patient-derived 3D co-culture model of tumor spheroids and T lymphocytes, image-based analyses allow the evaluation of lymphocyte infiltration and T cell-induced cytotoxic effects upon in vitro drug treatment; (2) together with our collaborators CPO and Charité, patient-derived 3D tumor cell cultures (PD3D) were subjected to in vitro drug testing, NGS panel sequencing and comprehensive proteomic analyses of several signal transduction pathways.

10:10 Networking Coffee Break

Phenotypic Screening of 3D Models

10:40 pm Chairperson’s Remarks

David Nolte, Ph.D., Professor, Physics, Purdue University; CTO, Animated Dynamics, Inc.

10:45 Implementing 3D Phenotypic and Target-Based Models to Interrogate Small Molecule Inhibition of the MAPK Pathway

Lesley Mathews Griner, Ph.D., Investigator II, Lab Head, Molecular Pharmacology, Oncology Research, Novartis Institutes for BioMedical Research

11:10 Phenotypic Screening for Cancer Therapeutic Efficacy in 3D Tissues

David Nolte, Ph.D., Professor, Physics, Purdue University; CTO, Animated Dynamics, Inc.

The three-dimensional cellular context is a key element influencing how cells respond to chemotherapeutics. Cellular adhesions, local membrane forces, intercellular signaling, and interactions with the extracellular matrix provide a microenvironment in which cancer proliferates and within which it responds to treatment. Biodynamic phenotypic profiling images dynamic processes deep inside 3D tissues, testing therapeutic efficacy in vitro while maintaining biological relevance, providing accurate measurements of individual response to therapy.

11:35 Label-Free Optical Molecular Imaging for in situ Viability Screening in 3D Engineered Tissues

Mary-Ann Mycek, Ph.D., Professor and Associate Chair for Translational Research, Department of Biomedical Engineering, College of Engineering & Medical School, University of Michigan

Noninvasive and label-free optical molecular imaging with metrics obtained from quantitative image analysis reliably screened viability in 3D living engineered tissues manufactured from primary human cells. Such optically derived metrics for tissue morphology and function could serve as quality control release criteria for cell-based tissue-engineered devices prior to implantation in patients, a critical regulatory requirement in regenerative medicine.

12:00 Close of Conference

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