(Shared Conference with World Preclinical Congress and IO Pharma Congress)

Cambridge Healthtech Institute’s 2nd Annual

Patient-Derived Tumor Organoids

Developing, Validating, and Scaling Tumoroids for Screening

June 19-20, 2019


Multicellular cancer “oids” (tumoroids, spheroids, organoids) provide models of intermediate complexity between standard two-dimensional culture systems and tumors in vivo. “Oids” exhibit physiologically relevant cell-cell and cell-matrix interactions, gene expression and signaling pathway profiles, heterogeneity and structural complexity that reflect in vivo tumors. When cultured properly, tumoroids form with relative ease and demonstrate the effectiveness, reproducibility, and robustness of this in vitro model system. Join preclinical researchers at Cambridge Healthtech Institute’s 2nd Annual Patient-Derived Tumor Organoids conference as they share case studies on fundamental tumor biology, host-tumor interactions, and the use of higher-throughput screening platforms for anti-cancer drug discovery and development

Final Agenda

Wednesday, June 19

12:00 pm Registration Open

NanosurfaceBiomedical 12:00 Bridging Luncheon Presentation to be Announced

12:30 Transition to Plenary


12:50 PLENARY KEYNOTE SESSION View details

2:20 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

TUMOROID GENERATION AND PROFILING FOR DRUG DEVELOPMENT

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 Human Tumor Organoids as a Novel Model for Drug Discovery and Screening

Wong_JanicaJanica Wong, PhD, Senior Scientist, Discovery Oncology, Merck Research Labs

Stem cell-derived organoids are self-organizing three-dimensional (3D) structures generated in vitro recapitulating the cellular architecture and functions of the tumor, which may be a more relevant model to study cancer biology. 3D in vitro tumoroids were established from human tumor tissues. Tumoroids transplanted into humanized mice produced tumors that resembled primary human tumors, suggesting organoids are a useful model for predicting drug responses with potential for use in precision medicine.

4:10 Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer

Tiriac_HerveHervé 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 Sponsored Presentation (Opportunity Available)

5:10 Networking Reception in the Exhibit Hall with Poster Viewing

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 View details

MICROFLUIDIC TECHNOLOGIES TO SCREEN FOR PATIENT SPECIFIC IMMUNOTHERAPIES

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

Ivanova_ElenaElena 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

jenkins_RussellRussell 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

Konry_TaliTania (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 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

FEATURED SESSION: ENABLING HIGH THROUGHPUT ANALYSIS

11:00 A PDX/Organoid Biobank of Advanced Prostate Cancer for Disease Modeling and Therapeutic Screening

kelly_kathleenKathleen 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

Scampavia_LouisLouis 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

Kamm_RogerRoger 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 Sponsored Presentation (Opportunity Available)

1:00 Transition to Lunch

1:05 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:35 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

EX VIVO MODELS FOR DRUG SCREENING

2:20 Chairperson’s Remarks

Aleksander Skardal, PhD, Assistant Professor, Wake Forest Institute for Regenerative Medicine

2:25 Human Patient-Derived Tumor Organoids: Ex Vivo Chemosensitivity Screening and Immune-Enhancing for Immunotherapy Responsiveness Screening

Skardal__ALexAleksander Skardal, PhD, Assistant Professor, Wake Forest Institute for Regenerative Medicine

Most in vitro models of human tumors are too simplistic and fail to accurately recapitulate the in vivo tumor microenvironment. This presentation will describe 1) the translation of bioengineered tumor organoid technology to support models derived from clinical tumor biospecimens for personalized ex vivo drug screening and therapeutic efficacy identification prior to treatment, and 2) immune-enhancing of such patient tumor organoids to support the ability to perform screens using immune checkpoint blockade therapies.

2:55 Pathomimetic Cancer Avatars as Preclinical Models for High-Content Analysis

Bonnie F. Sloane, PhD, Distinguished Professor of Pharmacology, Wayne State University School of Medicine

Preclinical models that recapitulate both cellular and pathochemical aspects of tumors and their microenvironment should accelerate identification of druggable pathways, screening of drug and natural product libraries and the entry of validated drugs or natural products into clinical trials. We have fabricated culture chambers to support growth of pathomimetic cancer models and developed live-cell, high-content imaging assays to quantify morphometry, viability and proteolysis and secretion of cytokines and chemokines.

3:25 Patient-Derived 3D Microtumors (PDMs) – A Versatile Platform for Compound Profiling and Efficacy Testing in Precision Oncology

schmees_christianChristian Schmees, PhD, Head of Tumor Biology, Molecular Biology Department, NMI Natural and Medical Sciences Institute at the University of Tübingen

A significant aspect of personalized cancer treatment is the integration of clinical with molecular data including multi-omics and functional analyses to assess individual signaling perturbations as vulnerabilities to tailored therapy. Patient-derived ex vivo models enable the implementation of this concept within a clinically relevant time frame. I will introduce our PDM platform co-cultured with autologous tumor-infiltrating lymphocytes (established for 11 human cancer types), and present data from transcriptomic and proteomic profiling as well as compound testing using chemo- and immunotherapeutics, and small molecules.

3:55 PANEL DISCUSSION: Translational Value of Preclinical Cancer Models: From PDXs to GEMMs and Organoids

Moderator: Alejandro Amador, PhD, GSK, Scientific Leader, Platform Biology Automation, GSK

Additional Speakers

  • Improving predictability and reliability
  • Co-clinical trials
  • Synergies

4:25 Close of Conference

Arrive early to attend Tuesday, June 18 - Wednesday, June 19

Preclinical Strategies, Models & Tools in Oncology

Recommended Short Course

SC3A: Development of Micro Physiological Systems for Drug Screening
SC10: In vitro and in vivo Modeling for Cancer Immunotherapy