(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.

Final Agenda

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 View details

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

TUMOR MODELS FOR CANCER IMMUNOTHERAPY

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

Joyce_BarbaraBarbara Joyce-Shaikh, 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 CRISPR-Based Models in Drug Discovery: Developments, Caveats and Future Perspectives

Danilo Maddalo, PhD, Lab Head, ONC Pharmacology, Novartis Institutes for BioMedical Research, Novartis Pharma AG

The development and the application of genome editing techniques in vivo has expanded the toolkit of preclinical models to assess drug efficacy and toxicology as well as the effect of compounds on tumour-microenvironment interaction. Cost and time-efficient, the talk will give an overview of CRISPR models, how they impacted significantly the workflow of preclinical drug discovery and their limitations and caveats.

4:10 Implantable Pre-Metastatic Niches for the Study of the Microenvironmental Regulation of Disseminated Tumor Cells

Lee-JungwooJungwoo 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 metastasis.

ProQinase_RBC 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 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

COMPLEX MODELS & IN VIVO SCREENING FOR ONCOLOGY TARGETS

8:10 Chairperson’s Remarks

John Doench, PhD, Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MIT

8:15 Use of in vivo CRISPR Screening in Drug Discovery

Danilo Maddalo, PhD, Lab Head, ONC Pharmacology, Novartis Institutes for BioMedical Research, Novartis Pharma AG

Identification of novel cell and non-cell autonomous targets has proven challenging as tumour cells display crucial differences in a 2D culture as opposed to an in vivo, 3D setting. To overcome such limitation, the ability to perform in vivo screening is key. I will give a brief overview of the current approaches to perform target identification and validation in in vivo models, their caveats and the future perspectives.

8:45 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.

9:15 From Co-Culture with Non-Cancerous Cells to the Production of Macrotumors: New Horizons for the Targeted Development of Anti-Cancer Therapy

lelievre_sophieSophie 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 Presentation to be Announced

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

Speakers of the Session

  • 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

SC7: Fit-for-Purpose Biomarker Assay Development and Validation
SC10: In vitro and in vivo Modeling for Cancer Immunotherapy