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 Inaugural Tumoroids for Oncology Research 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
Tuesday, June 19
7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)
8:15 Chairperson’s Opening Remarks
Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
8:20 Hyaluronan Hydrogels Enable 3D Culture of Cancer Cells and Drug Screening
Alexander Baker, Research Scientist, Molly Shoichet Laboratory, Institute of Biomaterials and Biomedical
Engineering, Chemical Engineering & Applied Chemistry, The Donnelly Centre, University of Toronto
We synthesized a series of hyaluronan-based hydrogels with either matrix metalloproteinase (MMP)-degradable or poly(ethylene glycol) (PEG) crosslinks, resulting in 3D networks that cells can remodel and invade. By controlling the chemical functionality
and modulus, we investigate their role on cell invasion and correlate that with drug response. We investigate a series of different cancer cell types, from breast and lung, and study their invasion into EGF-gradient and/or protein and peptide-modified
hydrogels.
8:50 Building Empirical Culture Technology to Facilitate Rare Cancer ex vivo Models at Scale
Moony (Yuen-Yi) Tseng, PhD, Group Leader, Research Scientist, Cancer Program, The Broad Institute of MIT and Harvard
It is challenging to access fresh rare tumor samples across a wide range of hospitals and we lack the ability to efficiently translate the limited biological knowledge that exists for most rare tumors into disease-specific model generation SOPs. By
partnering with foundations, social media to engage patients, and online consent, we have developed just-in-time biologistics to acquire fresh samples and empirically sample culture media space in a high-throughput, systematic manner to accelerate
ex vivo model generation in various rare cancers.
9:20 Air-Grown Lung Cancer Tumor Spheroids as a Novel in vitro Anti-Cancer Therapeutic Evaluation Platform
Samantha A. Meenach, PhD, Assistant Professor, Department of Chemical Engineering, Department of Biomedical
and Pharmaceutical Sciences, University of Rhode Island
Our research focuses on the development of air-grown multicellular spheroid (MCS) that mimic in vivo avascular tumors for the evaluation of aerosol anti-cancer therapeutics. Thus far, we have produced MCS
comprised of A549 lung adenocarcinoma cells that will be expanded to other cell lines in the future. This work involves the initial design of the technology and evaluation of MCS grown in this novel fashion. The growth kinetics, morphology, and
response to the model drug paclitaxel have been completed.
9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
10:35 Three-Dimensional Tumor Model Mimics Stromal–Breast Cancer Cells Signaling
Hossein Tavana, PhD, PEng, Associate Professor, Department of Biomedical Engineering, The University of Akron
Tumor microenvironment is a major contributor to tumor progression and is implicated in various stages of the disease. Using three-dimensional tumor spheroid models and molecular analysis, we demonstrate that CXCL12 (chemokine)–CXCR4 (receptor)
signaling between carcinoma-associated fibroblasts and breast cancer cells drives proliferation and chemotherapy resistance of the cancer cells. Disrupting this signaling diminishes growth drug resistance of breast cancer cells.
11:05 Clinically Relevant Patient-Derived Xenograft–Derived (PDXEx) ex vivo Model for Evaluation of Tumor-Specific Therapies
Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Translation of successful therapies into the clinics requires in vitro preclinical models that accurately predict the response of the original tumor to therapy. Our preclinical PDXEx model closely replicates
both the tissue architecture and genetic signature to the original tumor. We confirm the predictive value of our PDXEx model and demonstrate its importance as a platform for robotic-based high-throughput drug screens.
11:35 Screening and Profiling
of (Immuno-)Oncology Therapeutics in Primary and Stem Cell-Derived Human 3D Tissues
Leo Price, PhD, CEO, OcellO
Micro-tissues in a natural 3D extracellular matrix environment improve phenotype, function and gene expression compared to 2D cultures or spheroids grown absent of an ECM environment and therefore represent more relevant models for evaluating new
drugs prior to further studies. OcellO’s tissue models are based on PDX (Charles River Collection) patient-derived material, and cell lines combined with ultra-high content 3D image analysis. Phenotypic measurements allow better ranking
of therapeutic molecules.
12:05 Enjoy Lunch on Your Own
12:40 Session Break
1:15 Chairperson’s Remarks
Matthew M. Hewitt, PhD, Principal Scientist, Tumor Biology & Director, Tumor Immunology/Microenvironment, Research & Development, Bellicum Pharmaceuticals, Inc.
1:20 FEATURED PRESENTATION: Microenvironmental Context in Single and Collective Cell Migration
Cynthia Reinhart-King, PhD, Cornelius Vanderbilt Professor of Engineering, Biomedical
Engineering, Vanderbilt University
Metastatic migration is determined in large part by not only the cells but also the microenvironment through which cells must navigate. My lab focuses on the feedback between the cells and the extracellular matrix which drives migration decisions.
Using tissue-engineered models, ex vivo samples, and animal models, we have begun to dissect apart how structure and mechanics in the matrix mediate metastatic migration through key intracellular molecular
players.
1:50 Dynamic Reciprocity between Stromal Microenvironment and SOX2 Modulates Lung Cancer Cell Plasticity
Shuang Chen, PhD, Postdoctoral Fellow, Oncology Research Unit, Pfizer
Tumorigenesis depends on intricate interactions between the genetically altered tumor cells and their surrounding microenvironment. Our lab recently established a 3D co-culture system that enables mechanistic study of tumor-stromal interactions during
lung tumorigenesis. Using this model, we show that 1) lung squamous carcinoma cells are capable of phenotypic switching in response to cell intrinsic and extrinsic changes and 2) the tumor microenvironment could override cell intrinsic oncogenic
changes in determining the disease phenotype.
2:20 Exploring the Chemoresistance Mechanisms of Leukemia in a Biomimetic ‘Leukemia-on-a-Chip’ Microsystem
Chao Ma, PhD, Postdoc, Weiqiang Chen Laboratory, Department of Mechanical and Aerospace Engineering, New York University
Acute lymphoblastic leukemia (ALL) is the commonest pediatric malignance. The current survival rate of ALL for pediatric patients with chemotherapy is approaching 90%. However, no promising results have been observed in refractory ALL due largely
to chemoresistance. We herein explored in a 3D biomimetic ‘Leukemia-on-a-Chip’ how the leukemic bone marrow formed a supportive and protective vascularized niche to confer leukemia chemoresistance, highlighting the crucial role of
the BM niche in leukemia progression and therapy resistance.
2:50 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)
3:30 Optical Imaging of Anti-Cancer Drug Response of Organoids
Alex Walsh, PhD, Assistant Scientist, Department of Medical Engineering, Morgridge Institute for Research, University of Wisconsin - Madison
Primary tumor organoids are a robust model of individual human cancers and present a unique platform for patient-specific drug testing. Optical metabolic imaging (OMI) is highly sensitive to drug response in organoids, and OMI in tumor organoids correlates
with host survival. Therefore, functional optical imaging of organoids could enable accurate high-throughput screens of drug response for individualized cancer treatment.
4:00 Increasing CAR T Cell Efficacy in Solid Tumors via Understanding the Pro-Tumor Microenvironment
Matthew M. Hewitt, PhD, Principal Scientist, Tumor Biology & Director, Tumor Immunology/Microenvironment,
Research & Development, Bellicum Pharmaceuticals, Inc.
The talk focuses on challenges in developing CAR T cell therapies for solid tumors. A focal point will be describing a novel in vitro assay, cocultured with pro-tumor cell populations, and its use screening
lead preclinical candidates. The talk touches on translatability of in vitro assays to in vivo rodent systems and whether the use of molecular activation switches
can bypass pro-tumor immunosuppressive elements in the tumor microenvironment.
4:30 SELECTED POSTER PRESENTATION: Ru (II) Complexes and Two-Photon Photodynamic Therapy for Treatment of Human Melanoma
Ahtasham Raza, PhD, Research Associate, Materials Science & Tissue Engineering, Kroto Research Institute, University of Sheffield
5:00 Find Your Table and Meet Your Moderator
5:05 Interactive 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.
Preclinical CAR T Cell Development Challenges in Solid Tumors
Matthew M. Hewitt, PhD, Principal Scientist, Tumor Biology & Director, Tumor Immunology/Microenvironment, Research & Development, Bellicum Pharmaceuticals, Inc.
- Discuss the current assays available and their relevance
- Translatability of in vitro and in vivo systems to predict efficacy/safety
- Thoughts on how preclinical data translates to the clinic
5:45 Reception in the Exhibit Hall with Poster Viewing (America Ballroom)
7:00 Close of Day
Wednesday, June 20
7:45 am Registration Open (America Foyer) and Morning Coffee (Foyer)
8:25 Chairperson’s Remarks
Chao Zhou, PhD, Associate Professor, Founding Member, Department of Bioengineering, Department of Electrical and Computer Engineering, Lehigh University
8:30 Multi-Dimensional Biomaterial Screening Reveals Microenvironmental Mechanisms of Drug Resistance
Alyssa Schwartz, Graduate Research Assistant, Chemical Engineering, University of Massachusetts Amherst
We combined biomaterial platforms, drug screening, and systems biology to identify mechanisms of matrix-mediated resistance to RTK-targeted cancer therapies. Drug response varied with dimensionality and cell-cell contacts, and a systems analysis
identified MEK phosphorylation as the key factor associated with this variation. This uncovered the combination of sorafenib with a MEK inhibitor, which decreased viability in vitro and reduced tumor
burden, but was not captured by screening on plastic alone.
9:00 High-Throughput Optical Coherence Tomography Imaging for Drug Screening with 3D Tumor Spheroids
Chao Zhou, PhD, Associate Professor, Founding Member, Department of Bioengineering, Department of Electrical and
Computer Engineering, Lehigh University
Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anti-cancer drug development. However, currently available imaging approaches employed in high-throughput screening (HTS)
drug discovery platforms are unable to resolve 3D structures deep inside (>50 μm) tumor spheroids. In this study, we established a label-free, non-invasive optical coherence tomography (OCT) imaging platform to characterize 3D morphological
and physiological information of multicellular tumor spheroids.
9:30 A Novel High-Throughput Multi-Parametric Drug Screening Method for 3D Tumor Spheroids Using Celigo Image Cytometer
Leo Chan, Technology Research & Development Manager, Nexcelom Bioscience LLC
There is an increase in utilizing 3D spheroid for drug screening. We demonstrated a cancer drug scoring method using multi-parametric analysis to rank the anti-cancer effects of drugs on tumor spheroids. The assays conducted were growth inhibition,
perimeter cell-death, and viability. The drug can be screened to identify potential drug candidates.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
Essex South
10:45 CO-PRESENTATION: Creation of Patient Derived Cancer Models at Scale Leverages Patient Diversity for Improved Clinical Trials Predictions
Kin-Hoe Chow, PhD, Associate Director, Center for Patient Derived Models, Dana-Farber Cancer Institute
Keith L. Ligon, MD, PhD, Director, Department of Oncologic Pathology, Center for Patient Derived Models, Dana-Farber
Cancer Institute
In vitro and in vivo cancer models can now be created from a wide range of cancer types, yet the number of models created within each cancer and available widely in the cancer community remains low. Achieving a large number
of models in each disease requires large-scale generation of models to better predict the diversity of patient biology encountered in clinical trials. To address this, we have created a Center for Patient Derived Models within the academic
hospital setting to professionally support wide-scale model generation and creation of models specifically from patients who enter clinical trials. The Center currently aids investigators in studying more than 120 CNS models, 150 hematologic
models, and more than 100 other solid tumor models. Key advances include centralization and standardization of matching patient:model genotyping using targeted exome sequencing, matching of patient:model clinical outcomes, and entry of
large-scale cohorts of models more readily into preclinical screens in vitro and in vivo. Use of the Center is expected to foster new collaborations with industry, accelerated interpretation of clinical trial results,
and ultimately advance patient models into functional diagnostic tools within clinical pathology labs.
11:15 Human Tumor Organoids as a Novel Model for Drug Discovery and Screening
Janica Wong, PhD, Senior Scientist, Translational Pathology, 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, and 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.
11:45 Session Break
11:50 Bridging Luncheon Presentation: From Syngeneic to Humanized Mouse Models: Addressing the Needs for Novel Immunotherapies
Philippe Slos, PhD, Study Director, Oncodesign
Discovery of novel immunotherapy represents a main
and intense focus of research in oncology. Proof-of-concept studies in animals represent a challenge and require well-characterized and appropriate animal models with most of the time customized approaches. Some recent development and
data generated for immune checkpoint modulators, adoptive cell transfer therapy, vaccines and bispecific T cell engagers will be presented.
12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
1:00 PLENARY KEYNOTE SESSION
Essex South
Partnering for Sustainable Funding
The panel is designed to discuss partnering between various stake holders such as drug discovery startups, VC firms, large pharmaceutical companies and academic labs in order to advance new target discovery and preclinical research. VC companies,
and pharma search & evaluation departments will be represented on the panel.
Jens Eckstein, PhD, President, SR One
Barbara K. Sosnowski, PhD, Vice President and Global Head, External R&D Innovation, Pharmatherapeutics and WRD External Partnerships, Pfizer, Inc.
Kevin Bitterman, PhD, Partner, Atlas Venture
Vivian Berlin, PhD, Director of Business Development, Life Sciences, Office of Technology Development, Harvard University
Ben Thorner, Senior Vice President and Head, MRL Business Development & Licensing, Merck
Plenary Technology Panel
Advancing Innovation in Drug Discovery and Translational Research
This year’s Plenary Technology Panel features a group of technical experts from life science technology and service companies, who share their perspectives on various trends and tools that will likely change the way in which we traditionally
approach preclinical drug discovery and development. Attendees will have an opportunity to ask questions and understand the impact of recent technical advances.
Moderator: Leigh Zawel, PhD, Managing Director, MPM Capital
Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com
Stefan Braam, PhD, Technical Director, Ncardia
Mark Paris, PhD, Director, Translational Applications, Mitra Biotech
Edgard Wood, PhD, Senior Research Director, Discovery, Charles River
2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)
3:10 Close of Conference