(Shared Conference with World Preclinical Congress and IO Pharma Congress)
Cambridge Healthtech Institute’s 6th Annual
Cancer Immunotherapy Models
Predictable Cancer IO Models for Improved Translation
June 19-20, 2019
The demand for more predictive and robust preclinical models to minimize translational failure for oncology research, especially immune-oncology research, is at an all-time high. The need for leveraging phenotypic features of models and stimulating the
response of immune system adds to the complexity of preclinical models and their applications. Special emphasis is currently being placed on development and preclinical assessment of combination therapies and their rational preclinical design. Cambridge
Healthtech Institute’s 6th Annual Cancer Immunotherapy Models is designed to discuss cutting-edge, complex, immunocompetent models for cancer immunotherapy research as well as to present case studies of their successful applications.
Wednesday, June 19
12:00 pm Registration Open
12:00 Bridging Luncheon Presentation: New Insourcing and Outsourcing options PDX Tumors for Oncology Drug Discovery
Rick Huntress, Director, Commercial Business Development, JAX Mice and Clinical Research Services, The Jackson Laboratory
The Jackson Laboratory maintains a repository of over 400+ Patient Derived Tumors for PDX studies.Our open source interface allows researchers to review tumors by indication, genetic signature (NGS) , gene expression (RNASeq) and other parameters.
We'll review the common features of early passage tumors on study and provide helpful strategies for researchers interested in working with PDX tumors. We'll also present options for organizations to insource these tumors for their own discovery efforts.
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
Jungwoo Lee, PhD, Assistant Professor, Chemical Engineering Department & Institute for Applied Life Sciences, University of Massachusetts, Amherst
3:10 Human Immune System Development in Humanized Mouse Models: Latest Advances
Associate Principal Scientist, Merck Research Laboratories
Understanding the interactions between human immune cells and tumors is paramount when devising treatment strategies that prevent tumor evasion of immune cells and improve cytotoxic responses. In this talk we will discuss the generation of humanized
in vivo models to develop IO therapeutics and how we leverage humanized systems for deciphering mechanism of action and clinical translation. The limitations, predictive validity, and efficacy of will be discussed
as well as how humanized systems can replicate a more natural and translationally relevant tumor microenvironment.
3:40 Analysis of T Cell Engagers and Macrophage Repolarization Agents in a High Content 3D Tumor Co-Culture Platform
Gera Goverse, PhD,
The immune-oncology assays presented here allows the analysis of immunotherapy effects on different cell types that engage in a more physiologically relevant 3D setting. Visualization and quantification of these tumor-immune cell interactions offer
a highly powerful tool for cancer immunotherapy drug developers to discover the full potential of their compounds.
NEW: 4:10 Implantable Pre-Metastatic Niches for the Study of the Microenvironmental Regulation of Disseminated Tumor Cells
Jungwoo Lee, PhD,
Assistant Professor, Chemical Engineering Department & Institute for Applied Life Sciences, University of Massachusetts, Amherst
Many cancer survivors carry disseminated tumor cells but do not experience relapse due to tumor cell dormancy. Understanding how the local microenvironment regulates the transition from this quiescent state to active proliferation could lead to new
therapeutic strategies to prevent or delay metastases. In this talk, I introduce a new approach to study in vivo metastasis by combining a tissue-inspired, implantable, biomaterial microenvironment and existing mouse model for studying
NEW: 4:40 Novel Syngeneic Tumor Models Featuring Conserved Stroma and Immune Cell Profiles
Katrin Schlie, Business Development Manager, ProQinase
We have generated new syngeneic tumor models suitable for drug testing which were derived from spontaneous or carcinogen-induced mouse tumors and were aptly named Mouse-Derived Isograft Models (MDI). They are propagated in mice in a PDX-like fashion
and therefore contain conserved tumor-stroma characteristics and immune cell profiles.
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
8:10 Chairperson’s Remarks
John Doench, PhD, Associate Director, Genetic Perturbation
Platform, Broad Institute of Harvard and MIT
8:15 NEW: Application of CRISPR Technology to in vivo Models of Cancer Immunotherapy
John Doench, PhD, Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MIT
CRISPR screens have become the method of choice for large-scale assessment of gene function, but implementation in complex model systems remains a significant challenge. Here I will present the optimization of mouse models to discover modulators
of tumor immunotherapy. Combinatorial screens present similar challenges and will also be discussed.
8:45 NEW:Large Scale Proteomics Approaches to Accelerate Degrader Development
Katherine Donovan, PhD, Scientist, Laboratory of Dr. Eric Fischer, Cancer Biology, Dana-Farber Cancer Institute/Harvard Medical School
9:15 From Co-Culture with Non-Cancerous Cells to the Production of Macrotumors: New Horizons for the Targeted Development of Anti-Cancer Therapy
Sophie Lelievre, DVM, PhD, LLM, Professor, Cancer Pharmacology, Purdue University College of Veterinary Medicine
In vitro production of tumors is paramount to improve target identification and drug testing compared to classical monolayer culture. However, the microenvironment ought to be considered to best recapitulate conditions
promoting tumor progression and resistance to treatment. Tumor size also matters to reproduce intermittent oxygenation and the proper ratio of tumor and stromal cells. I will present how 3D cell culture might be used for the identification
of targets to fight anti-cancer drug resistance.
9:45 ZeGenesis: CRISPR/Cas9 Innovative Zebrafish Platforms for Disease Modelling and Target Validation
Flavia De Santis, R&D, Scientist, Scientific department, ZeClinics
Zebrafish is rapidly imposing itself as a powerful model to understand human disease. Recently, the implementation of CRISPR/Cas9-based techniques for targeted gene manipulation enhanced the use of this animal in pharmaceutical research.We have
developed ZeGenesis, a platform for the phenotypic characterization of candidate genes potentially involved in a pathological conditions. We present how the use of the zebrafish in the drug-discovery process, can reinforce preclinical studies,
allowing reliable disease modeling and fast target validation.
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
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 with Potential Partners and Collaborators!
2:20 Chairperson’s Remarks
Alejandro Amador, PhD, GSK, Scientific Leader, Platform Biology Automation, GSK
2:25 Pathomimetic Cancer Avatars as Preclinical Models for High-Content Analysis
Raymond R Mattingly, PhD, Professor and Chair 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.
2:55 Patient-Derived 3D Microtumors (PDMs) – A Versatile Platform for Compound Profiling and Efficacy Testing in Precision Oncology
Christian 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.
3:25 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
Panelists: Christian Schmees, PhD, Head of Tumor Biology, Molecular Biology Department, NMI Natural and Medical Sciences Institute at the University of Tübingen
Barbara Joyce-Shaikh, Associate Principal Scientist, Merck Research Laboratories
Kathleen Kelly, PhD, Lab Chief, Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute
Zhao Chen, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)
- Improving predictability and reliability
- Co-clinical trials
4:25 Close of Conference