- 癌症免疫治疗的肿瘤模型 -

Today immune-mediated therapy is a mainstream approach to many cancer types, and the demand for predictive and robust preclinical models to minimize translational failures in immuno-oncology 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 being currently placed on development and preclinical assessment of combination therapies and their rational preclinical design. Cambridge Healthtech Institute's Fifth Annual Tumor Models for Cancer Immunotherapy is designed to feature and 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 20

11:00 am Registration Open

11:50 Bridging Luncheon Presentation: From Syngeneic to Humanized Mouse Models: Addressing the Needs for Novel Immunotherapies

Francis Bichat, Head, In Vivo Sciences, 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


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


3:10 Chairperson's Opening Remarks

Zhao Chen, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research

3:15 KEYNOTE PRESENTATION: Ex vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

David Barbie, MD, Assistant Professor, Medical Oncology, Dana-Farber Cancer Institute

Just as precision cancer medicine has been essential to the successful development of oncogene-targeted therapies, it will be equally essential to deploy next generation immunotherapies in a targeted fashion and develop personalized combinations. To this end, our laboratory has developed and initially validated microfluidic 3-dimensional (3D) culture of patient-derived or murine-derived organotypic tumor spheroids (PDOTS/MDOTS) as a means of assessing the ex vivo response to PD1 immune checkpoint blockade.

3:45 Utilizing 3D Models for Cancer Stem Cell Target Validation and Drug Discovery

Anita Seshire, PhD, Lab Head, Cellular Pharmacology, Translational Innovation Platform Oncology, Merck KGaA

Tumor spheres are three-dimensional structures that spontaneously form under non-adherent and serum free conditions. Sphere formation is an exclusive function of tumor initiating cells (cancer stem cells). We show how to utilize 3D-spheres for in vitro and in vivo models for therapeutic antibody validation.

4:15 Sponsored Presentation (Opportunity Available)


4:45 CRISPR/Cas9 in Preclinical and Drug Discovery

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

The generation of preclinical models faithfully recapitulating genetic lesions found in patients represents one of the major limitations in drug discovery. In this talk, I will discuss the methods for generating preclinical animal models, what we can learn from such models in the process of drug discovery and target identification, and the future perspective of the CRISPR/Cas9 in pharma industry.

5:15 In vivo CRISPR Screen to Identify Immune Modulators in Tumor Cells

Zhao Chen, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research

Target ID by in vivo genetic screens is particularly suitable for identification of immune modulatory targets due to the dynamic nature of the tumor microenvironment, on condition that the screen was designed and controlled carefully. We have obtained some insights on this topic over the past couple of years on a few key factors contributing to a successful in vivo screen.

5:45 Close of Day and Dinner Short Course Registration*

*Separate registration required.

Thursday, June 21

7:30 am Registration Open and Morning Coffee


8:00 Chairperson's Remarks

Andrew Whale, PhD, Senior Scientist, Manager, Preclinical, Immunocore Ltd.

8:05 KEYNOTE PRESENTATION: Translational Approaches for CAR T Cell Therapy Development

Jennifer Brogdon, PhD, Director, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research

T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. Understanding the complex tumor microenvironment and the initial T cell starting material may afford greater insights into parameters which potentially influence CAR T cell efficacy and safety.

8:35 An in vitro Preclinical Package to Assess the Safety and Efficacy of Immtac™ Molecules Alone or in Combination

Andrew Whale, PhD, Senior Scientist, Manager, Preclinical, Immunocore Ltd.

ImmTAC molecules are soluble pico-molar affinity TCRs fused to an anti-CD3 scFv domain that recognise tumour antigen peptides presented by MHC-I and re-direct T cells, mediating tumour cell killing. As ImmTAC molecules are human specific, traditional in vivo models are unsuitable to evaluate safety and efficacy. We present how Immunocore's in vitro preclinical package has approached the challenge to assess ImmTAC molecules as monotherapy and combination agents.

9:05 Transforming Translational Research: CANscript™ - A Better Predictive Model for Oncology

Mark Paris, PhD, Associate Director, Translational Applications, Mitra Biotech

Mitra Biotech has developed and clinically validated our human ex vivo tumor platform technology (CANscript™). CANscript uses patient material (tumor, autologous ligands and PBMC) to explore the mechanism of action and predict efficacy for clinically-directed compounds in a modality-agnostic way using phenotypic effects. This talk will explore how CANscript was used to model the effect of checkpoint inhibition in HNSCC to identify predicted clinical responders and uncover mechanisms of resistance.

9:35 Find Your Table and Meet Your Moderator

9:40 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.

Modeling Innate and Adaptive Immunity in Murine Models

Marcus Bosenberg, MD, PhD, Associate Professor of Dermatology and Pathology, Yale University, Co-Leader, Genomics, Genetics and Epigenetics Program, Yale Cancer Center

  • Can animal models of cancer immunology predict human responses?
  • How should pre-clinical models be used to guide drug development in immunology?
  • How can existing models be improved?

Emergence of Microfluidic Models for Preclinical Assessment of Efficacy of Immune Checkpoint Inhibitors

Jeffrey Borenstein, PhD, Laboratory Technical Staff, Biomedical Microsystems, Draper

  • Immune checkpoint inhibitors exhibit variable patient response rates for reasons that are not completely clear. What attributes of an in vitro model are seen as most critical for establishing it as a tool to study mechanisms of responder/non-responder behavior?
  • Microfluidic model systems may find use as tools for drug development and ultimately for precision medicine applications, where patient response could be predicted before administering therapy. Where are the most significant opportunities for these systems, and would the attributes models for each respective application be different?
  • Many existing in vitro cancer models are cell culture systems, where cancer cells are cultured in a 3D microenvironment. Emerging systems are focusing on tumor spheroids and on unmodified tumor fragments obtained from patient (or animal) biopsy. What are the principal advantages and disadvantages of each type of model?

10:20 Coffee Break in the Exhibit Hall with Poster Viewing


11:05 Optimized Syngeneic Models of Anti-Cancer Immune Responses

Marcus Bosenberg, MD, PhD, Associate Professor, Dermatology and Pathology, Yale University, Co-Leader, Genomics, Genetics and Epigenetics Program, Yale Cancer Center

The success of immune therapies in cancer has underscored the need for accurate pre-clinical models for the evaluation of novel therapies. We have generated a series of genetically diverse syngeneic melanoma cell lines that form tumors following injection into immune competent C57Bl/6J mice. These models represent an ideal set of tools for the study of cancer immunology and response to immune therapies.

11:35 huPBMC Donor Selection for Humanized Mouse Model

Fangxian (Frank) Sun, Lead Research Investigator, Pharmacology, Sanofi

NOD-scid IL2Rgammanull, NSG mice engrafted with functional human cells and tissues, i.e., "humanized mice", have become increasingly important as small pre-clinical animal models for the study of human diseases. Scientists have been able to engraft murine recipients with human hematopoietic stem cells or peripheral blood mononuclear cell (PBMC) that reconstitute functional human immune systems. These mice can also be engrafted with human tissues such as solid and hematologic cancers. Humanized mice are permitting significant progress in studies of human cancers. We characterized human PBMCs in vivo and in vitro from dozens of human donors. This information provided criteria for huPBMC donor selection for humanized mouse model.

12:05 pm Human Immune System Development in Humanized Mouse Models: Latest Advances

Barbara Joyce-Shaikh, Associate Principal Scientist, Merck Research Laboratories

RTK inhibitors have significantly prolonged non-small cell lung cancer patient survival, but the development of resistance limits the durability of clinical response. One potential strategy to enhance the durability of response to targeted therapies is to couple them with immunotherapy. We hypothesized that the small molecule inhibitor of FGFR, Erdafitinib-mediated tumor cell death and antigen release could prime and activate T-cell responses, and that combination with T-cell directed checkpoint blockade would further enhance antitumor immunity and enhance the durability of response.

12:35 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing


1:55 Chairperson's Remarks

Marco Ruella, MD, Clinical Instructor, Associate Director, Dr. June's Laboratory, Center for Cellular Immunotherapies (CCI), Perelman School of Medicine, University of Pennsylvania

2:00 Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer

Marco Ruella, MD, Clinical Instructor, Associate Director, Dr. June's Laboratory, Center for Cellular Immunotherapies (CCI), Perelman School of Medicine, University of Pennsylvania

Adoptive T cell therapies, and in particular chimeric antigen receptor T cells (CART), are leading to significant responses in cancer patients, in particular B-cell leukemias and lymphomas. New gene editing technologies, like CRISPR-Cas9, can offer an exciting tool for the manipulation of T cells to increase their feasibility and efficacy.

2:30 Preclinical Development of Dual-Switch CAR-T Cells for Cancer Therapy: Independent Control T Cell Efficacy and Safety with Small Molecules and Protein Switches

J. Henri Bayle, PhD, Director of Discovery, Bellicum Pharmaceuticals, Inc.

Chimeric Antigen Receptor (CAR)-based cell therapies show efficacy against disseminated cancers, but control over toxicity or activation can temper utility, particularly against solid tumors. We will describe preclinical studies of two distinct dual-control platforms that include ligand-inducible activation or apoptosis of T-cells, comprising inducible iMyD88/CD40 and iCaspase-9 components. These animal studies show exquisite dual-switch control of T cell expansion or contraction along with tumor control using non-crossreacting, clinical-grade ligands.

3:00 Developing Small Molecule Immune Checkpoint Inhibitors: Opportunities and Insights

Adam S. Lazorchak, PhD, Senior Scientist, Immunology & Translational Sciences, Curis, Inc.

Small molecules targeting immune inhibitory checkpoint pathways offer unique therapeutic opportunities relative to antibody based therapies, including the ability to target a broader range of extracellular or intracellular motifs and precisely control drug exposure to enhance safety. I will discuss Curis's pre-clinical development of oral small molecule checkpoint inhibitors, emphasizing novel questions relating to immune checkpoint biology that we are addressing with our specific small molecule checkpoint inhibitors.

3:30CO-PRESENTATION: Dynamic Microfluidic Model for Predicting Tumor Response to Immune Checkpoint Inhibitors

Jeffrey Borenstein, PhD, Laboratory Technical Staff, Biomedical Microsystems, Draper

Hongmin Chen, PhD, Principle Scientist, Pharmacology, Merck

Current systems to assess tumor response to immune checkpoint inhibitors are limited to static culture systems and short duration studies. Here we report on progress toward a high throughput microfluidic system for assessing rodent and human tumor response to immune checkpoint therapy by recapitulating the dynamics of the immune microenvironment. This system permits real-time visualization of tumor-infiltrating lymphocyte (TIL) interactions with tumor biopsy samples and quantification of TIL infiltration and tumor killing.

4:00 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 12: Humanized Mouse Models for Preclinical Assessment of Cancer Immunotherapy

Conference: Preclinical Strategies, Models & Tools in Oncology or Tumoroids for Oncology Research

Conference: Tumor Models for Cancer Immunotherapy

2018 World Preclinical Congress CAG Brochure icon

* 活动内容有可能不事先告知作更动及调整。