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- 肿瘤学研究的癌症Tumoroid -

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 and Morning Coffee

ENGINEERING MODELS & APPLYING PLATFORMS

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 FEATURED PRESENTATION: Hyaluronan Hydrogels Enable 3D Culture of Cancer Cells and Drug Screening

Molly_ShoichetMolly S. Shoichet, PhD, FRSC, O. Ont., University Professor and Canada Research Chair, Tissue Engineering; Chemical Engineering & Applied Chemistry, 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_MeenachSamantha 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

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 Sponsored Presentation (Opportunity Available)

12:05 pm Session Break

12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:40 Session Break

MODELING THE TUMOR MICROENVIRONMENT

1:15 Chairperson's Remarks

Anna L. Means, PhD, Associate Professor, Department of Surgery, Vanderbilt University Medical Center

1:20 FEATURED PRESENTATION: Microenvironmental Context in Single and Collective Cell Migration

Cynthia_Reinhart-KingCynthia 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_ChenShuang 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 Sponsored Presentation (Opportunity Available)

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing

3:30 Using Tumoroids to Understand Cell-Cell Signaling Roles in Cancer

Anna_MeansAnna L. Means, PhD, Associate Professor, Department of Surgery, Vanderbilt University Medical Center

We found that the healthy colon uses TGF-beta signaling to suppress production of chemokines and cytokines by colon epithelium, thereby regulating cell-cell interactions. When this regulation by TGF-beta is blocked specifically within colon epithelium, mice become susceptible to inflammation-induced carcinogenesis. We are now using human tumoroids to investigate the ability of TGF-beta to alter chemokine and cytokine production by colon cancer epithelium that then alters the microenvironment surrounding it.

4:00 Increasing CAR T Cell Efficacy in Solid Tumors via Understanding the Pro-Tumor Microenvironment

Matthew_HewittMatthew 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 Startup Spotlights

Explore emerging 3D cellular models and the screening platforms as presented by startup companies. This is an unparalleled opportunity to compare and contrast promising platforms to best suit your R&D needs.

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

Tumoroid/Microenvironment Interactions: Possibilities and Limitations

Anna L. Means, PhD, Associate Professor, Department of Surgery, Vanderbilt University Medical Center

5:45 Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day

Wednesday, June 20

7:45 am Registration Open and Morning Coffee

SCREENS TO PREDICT DRUG RESPONSE

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_SchwartzAlyssa 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_ZhouChao 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

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, Center for Patient Derived Models, Department of Oncologic Pathology, 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 (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing


1:00 PLENARY KEYNOTE SESSION

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

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.

Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com

Additional Panelists will be Announced

Sponsorship Opportunities Available

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing

3:10 Close of Conference


Recommended Event Package

Short Course 6: Collecting, Storing, and Utilizing Precious Patient-Derived Tumors for Drug Discovery and Development

Short Course 9: How to Best Utilize 3D Cells, Spheroids, PDX Models in Oncology

Short Course 14: Advanced Bioprinting Strategies for Generation of 3D Tissue Models

Conference: Tumoroids for Oncology Research

Training Seminar 6B: Patient-Derived ASC-Organoids for Drug Development and Screening, Patient Stratification and Regenerative Medicine


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