2018 Archived Content

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Cambridge Healthtech Institute’s 3rd Annual

Preclinical and Translational Immuno-Oncology

Predictive Preclinical Models and Translational Strategies for Cancer Immunotherapy

August 28-29, 2018

The recent advancements in immunotherapies, such as immune checkpoint modulators, bispecific antibodies, and adoptive T cell transfer, are shifting the way cancer patients are treated. Rapid development of novel immuno-oncology programs is creating the need for predictive preclinical models and translational strategies to understand combination immunotherapy, study responses and resistance to cancer immunotherapy, and identify novel biomarkers and targets. Please join Cambridge Healthtech Institute’s Third Annual Preclinical and Translational Immuno-Oncology meeting and learn about new clinically-relevant models for screening IO therapies and translational strategies to support clinical IO programs.

Final Agenda

TUESDAY, AUGUST 28

12:00 pm Registration (Harbor Level)

1:25 Chairperson’s Opening Remarks

William Hastings, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis

1:30 FEATURED PRESENTATION: Defining the Difference: Developing Translational Screening Models to Mimic Tumor Microenvironment

Litao Zhang, PhD, Vice President, Leads Discovery and Optimization, Bristol-Myers Squibb

2:00 Utilizing 3D Immune/Tumor Cell Co-Culture Systems for Evaluation of IO Therapies

William Hastings, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis

2:30 Beyond Genomics: Multiplex Protein Profiling for Biomarker Identification

Christoph Sachse, PhD, Site Head Berlin, NMI TT Pharmaservices

Our approach is to employ comprehensive multiplex protein profiling for lead compound characterization, biomarker identification and precision medicine development. Using the DigiWest technology, we analyze up to 800 total and phospho proteins from cell or tissue samples, thus adding considerable value beyond genomics profiling. We will present data from studies on chemotherapy resistance biomarkers and in primary patient-derived 3D tumor organoids (PD3Ds).

3:00 Automation and Decentralization of CAR-T Cell Manufacture

Dropulic_Boro Boro Dropulic, PhD, CSO & General Manager, Administration, Lentigen Technology, Inc., A Miltenyi Biotec Company

Adoptive T-cell immunotherapy for the treatment of hematologic malignancies have highlighted the need for manufacturing processes for gene-modified cellular therapies. Automation of cell processing and scale up of Lentiviral vector manufacturing are highlighted. A decentralized manufacturing network is being implemented: patients’ cells are processed locally at the patient care site.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

4:15 PLENARY KEYNOTE SESSION (Cityview 1)

4:20 CAR-T Therapy for B Cell Malignancies

Jennifer Brogdon, PhD, Director, Exploratory Immuno-Oncology, Novartis

Catherine Young 4:55 Walking on the Moon: Reflections on the Work of the Cancer Moonshot and the Future of the Biden Cancer Initiative

Catharine Young, PhD, Senior Director, Science Policy, Biden Cancer Initiative

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

5:30 Dinner Short Course Registration* (Harbor Level)

*Separate registration required.

6:30 End of Day

6:30-9:00 pm Dinner Short Course

SC1: Bioinformatics for Immuno-Oncology and Translational Research

6:30-9:00 pm Dinner Short Course

SC2: Next-Generation Immunotherapies: Part 1

WEDNESDAY, AUGUST 29

7:30 am Morning Coffee (Harbor Level)

8:25 Chairperson’s Remarks

Marcus Bosenberg, MD, PhD, Professor, Dermatology, Pathology, and Immunobiology, Yale University

8:30 FEATURED PRESENTATION: The Role of Genetically Engineered Mouse Models of Cancer in Profiling Novel Immune Targeting Therapies

Elizabeth Hardaker, PhD, Head, Oncology In Vivo Pharmacology, AstraZeneca

Immune oncology targets are expanding to include multiple cell types, including T cells and myeloid cells. Syngeneic models are useful for profiling some novel immune targeting agents; however, there are some targets and combinations that are not relevant in these models. To understand where the models have utility, we need to have a good understanding of the tumor microenvironment. New model systems are also required to effectively profile novel immune oncology therapies and combinations. In this presentation, the kinetics of the immune response within 3 commonly used syngeneic models (CT26, MC38, 4T1) will be described.

9:00 NEW: Gaining Preclinical Insight on Tumor Infiltrating B Cells in Tertiary Lymphoid Structures of Patient Primary Tumors

Tullia Bruno, PhD, Assistant Professor, Immunology, University of Pittsburgh and Hillman Cancer Center

9:30 Mouse Syngeneic Models: Biological Variability in Response to Therapy and Underlying Cellular and Molecular Factors

Fadden_Patrick Patrick Fadden, Research Director, Charles River

Mouse Syngeneic Models: Biological Variability in Response to Therapy and Underlying Cellular and Molecular Factors Involved" Syngeneic models have greater animal to animal variability as well as inter-study variability than standard xenograft models. We will discuss potential biological explanations for this, the relationship between gene expression changes and individual animal response and practical implications for study design and interpretation.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

10:45 Using Mouse Models to Dissect Different Components in the Tumor Microenvironment

Zhao Chen, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institute of Biomedical Research

The tumor microenvironment web largely determines the fate of tumor initiation, progression and treatment responses. Faithful in vivo analyses are powerful tools to pinpoint the critical nodes in this dynamic network. Further, in vivo genetic screens and subsequent target validation using appropriate in vivo models are also keys in identifying immune modulatory targets.

11:15 Modeling Dysfunctional T-Cell Immunity of Tumor in Mouse

Hiroshi Nakashima, PhD, Instructor, Neurosurgery, Brigham & Women’s Hospital, Harvard Medical School

11:45 Preclinical Testing of Anti-Cancer Immune Therapies

Marcus Bosenberg, MD, PhD, Professor, Dermatology, Pathology, and Immunobiology, Yale University

Efforts to improve immune-oncology therapies in the setting of low response rates or resistant disease would benefit from human-relevant models that accurately predict responses to new and combinatorial immune therapies. The evaluation of anti-cancer immune therapies using cutting-edge immunogenic mouse models will be presented. In addition, future directions in modeling and correlative analyses will be discussed.

12:15 pm Luncheon Presentation: Transforming Translational Research: CANscript™ - A Better Predictive Model for Oncology

Paris_Mark Mark Paris, PhD, Director, Translational Applications, Biopharma Business Development, Mitra Biotech, Inc.

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.

12:45 Session Break

1:40 Chairperson’s Remarks

Genevieve Boland, MD, PhD, Director, Melanoma Surgery Program, Massachusetts General Hospital; Director, Surgical Oncology Research Laboratories, Massachusetts General Hospital; Assistant Professor, Harvard Medical School; Associate Member, Broad Institute

1:45 Genetic Alterations in CD19 Lead to CD19 Negative Relapse to CAR19 Therapy in Pediatric Acute Lymphoblastic Leukemia

Elena Orlando, PhD, Bioinformatics Investigator, Novartis Institutes for BioMedical Research

Despite remarkable responses following CAR T-cell therapy in ALL, relapse poses a significant threat. We used next-generation sequencing to study the mechanisms of CD19 negative relapse. We found that all CD19 negative relapse patients evaluated acquired genetic alterations that explain their loss of CD19 protein expression. These findings suggest retreatment strategies likely to be most effective in this setting.

2:15 Genomic and Immunologic Changes Associated with Immune Checkpoint Blockade In Melanoma

In melanoma, there is extensive experience treating patients with immune checkpoint therapies (ICT). Longitudinal profiling and patient-derived samples have allowed us to identify genomic, transcriptomic, and epigenetic changes associated with response to therapy and distinct immune changes in patients treated with ICT. This presentation will highlight known and emerging tumor and immune changes associated with response and/or resistance to ICT and identify new areas of investigation and approaches to therapy.

2:45 Utilizing Sophisticated Mouse Models to Better Understand the Pathways and Mechanisms of Emerging Immune Therapies

Rick Huntress, Director, Business Development, The Jackson Laboratory

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

4:00 COX2-PGE2-Orchestrated Secondary Suppression in the Course of Immunotherapy

Pawel Kalinski, MD, PhD, Professor, Oncology, Vice-Chair, Translational Research, Roswell Park Cancer Institute

Immune checkpoint blockade (ICB) provided effective treatment option for many types of advanced cancer, but the majority of cancer patients show primary or secondary resistance to ICB. The effectiveness of ICB and other forms of cancer immunotherapy is regulated at the level of tumor microenvironment (TME) by the balance between type-1 effector cells, such as CD8+ cytotoxic T cells (CTLs), Th1 and NK cells and suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). We observed the activation of CTLs or NK cells in the TME of human cancers results in a strong mobilization of PD-1-independent “secondary” suppression, mediated by activated MDSCs.

4:30 Cross-Talk among Distinct Immune Regulatory and Effector Cells in Cancer in Different Tissues

Jay A. Berzofsky, MD, PhD, Chief, Vaccine Branch, Center for Cancer Research, National Cancer Institute

We found that the same tumor growing in the lung or skin has different immunoregulatory mechanisms that inhibit immunosurveillance, even when both tumors are growing in the same animal. The effector cells that protect when the regulatory cells are removed also cross talk in only one direction, from skin to lung but not vice versa. Thus, even for the same tumor, one must overcome different immunoregulatory mechanisms for immunotherapy in the primary tumor or in lung metastases, which is an important finding for cancer immunotherapy.

5:00 Development of Combination Strategies to Improve the Efficacy of Cancer Immunotherapy

McKenzie_Jodi Jodi McKenzie, PhD, Senior Clinical Research Scientist, Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center