We are witnessing the renaissance of the concept of immune-mediated cancer therapy, 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 Fourth 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 14
11:00 am Registration
12:00 pm Bridging Luncheon Presentation: Combination Immune Checkpoint Inhibitors for the Treatment of Solid Tumors in Humanized Mouse Models
Paula Miliani de Marval, Ph.D., Research Associate Director,
Charles River
The increasing success and interest in cancer immunotherapy, there is a growing need for relevant preclinical models. Our studies with syngeneic tumors, using immune checkpoint inhibitors targeting CTLA-4 and PD-1, showed differential responses
across tumor types. We have evaluated the efficacy of these inhibitors on human tumor xenograft models implanted in CD34+ and PBMC humanized mice. Results from these studies shows significant tumor growth inhibition associated with T cell
activation.
12:30 Session Break
1:00 Coffee and Dessert in the Exhibit Hall with Poster Viewing
1:30 PLENARY KEYNOTE SESSION
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Chairperson’s Opening Remarks
Gary C. Starling, Ph.D., Associate Vice President, MRL Biologics and Vaccines Discovery, Merck
4:25 KEYNOTE PRESENTATION: Increasing the Efficacy of Immunotherapy with Combinatorial Approaches
Gary C. Starling, Ph.D., Associate Vice President, MRL Biologics and Vaccines Discovery, Merck
Immunotherapy using monoclonal antibodies against the checkpoint inhibitors CTLA-4 and PD-1 have shown dramatic clinical success. To increase therapeutic efficacy in sensitive tumor types or to treat tumors that are resistant to targeting single
immune check point inhibitors, combinations of agents are being evaluated. The rationale behind the selection of combination agents will be discussed along with examples of the impact of these combinations.
4:55 Augmented Response to Anti-PD1 Therapy by Co-Blockade of LAG3 in Immune Competent Mouse Models of Cancer
Brian B. Haines, Ph.D., Principal Scientist, Pharmacology, Merck
5:25 Novel Humanized Mouse Models in Immuno-Oncology: Applications and Production Consistency
Azusa Tanaka, Ph.D., Product Manager, Precision Research Model, Taconic Biosciences
Humanized mice reconstituted with human hematopoietic stem cells (HSC) mimic human immune responses, supporting translatable research into pathophysiology, immuno-oncology, and novel therapeutic methodologies. Reservations remain regarding
reproducibility, HSC sourcing, and the stability of chimeric cells in humanized mice. To address these concerns, Taconic presents data supporting the consistency, reliability, and chimeric ratios for over 1500 production huNOG (humanized
NOG) and over 800 huNOG-EXL (humanized hGM-CSF/hIL-3 NOG) from Taconic production colonies.
5:55 Is Translation Even Necessary? Dose Prediction in the Absence of Validated Preclinical Models
Arijit Chakravarty, Ph.D., CEO, Fractal Therapeutics
This talk will discuss the problem of dose prediction for IO, with broader applicability beyond that.
6:25 Close of Day
6:30 Dinner Short Course Registration
Thursday, June 15
7:00 am Registration Open and Morning Coffee
7:30 Interactive Breakout Discussion Groups with Continental Breakfast
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. Continental breakfast is available for all participants.
Modeling Innate and Adaptive Immunity in Murine Models
Moderator: Marcus Bosenberg, M.D., Ph.D., 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?
Preclinical Strategies for Combination Strategies
Moderator:
Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis
Institute of Biomedical Research
- Key factors to consider when selecting combination strategy
- Immunomodulatory effects of small molecules
- Translating preclinical models to the clinic-the expected and unexpected
T Cell Therapy
Moderators:
Simrit Parmar, M.D., Assistant Professor, Department of Stem
Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Ian McNiece, Consultant, CellMED Consulting (CMC)
- The use of small animal models for preclinical studies of immune effector cells
- The advantages and disadvantages of small animal models vs large animal models for studies of T cell products
- The use of immune suppressed animals versus immune deficient animals
8:35 Chairperson’s Remarks
Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis Institute of Biomedical Research
8:45 Leveraging Immunophenotypic Features of Preclinical Models to Minimize Translational Failures
Mithun Khattar, Ph.D., Immuno-Oncology Lead, Cancer Pharmacology, Takeda Pharmaceuticals
Syngeneic model systems that provide a wide array of B-cell, Myeloid cell and NK cell mediated tumor-immune milieus with a varying degree of T-cell involvement can help researchers to hone in on the MoA questions. Such a preclinical
exploration can then help us with patient selection hypotheses and also potential combination scenarios. The future for IO therapy most likely is going to be targeting multiple facets of immune suppression which could be decided
based on prior chemotherapies.
9:15 Genotype, Tissue Type and Tumor Microenvironment
Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis Institute
of Biomedical Research
Cancer cells play key roles in shaping up the tumor microenvironment. Cancer genetic studies also tell us that much of the behavior of the tumor is dictated by genetic alterations and tissue origin. However, the link is missing between
these tumor cell autonomous traits and their corresponding influence on tumor microenvironment. We are interested in charactering genotype and tissue type dependency of tumor microenvironment, and its relevance to treatment responses.
9:45 3D Spheroid Models of Fresh Patient Tumors: Ex vivo Analysis of Immune Microenvironment and Rational Combination Therapy
Soner Altiok, MD, Ph.D., CSO, Nilogen Oncosystems
Nilogen’s 3D-EX℠ immuno-oncology platform utilizes fresh patient tumor tissue with intact tumor immune microenvironment. With the capability to analyze the intimate interactions between the immune system and components of
cancer tissue we can accurately assess the therapeutic efficacy of drugs, identify rational drug combinations and develop companion diagnostics to facilitate biomarker-driven drug development efforts and personalized medicine
while reducing the cost and risk of bringing a new drug to market.
10:00 Predictive Single-Cell Response Applied to Immuno-Oncology
Sean Mackay, CEO, IsoPlexis
IsoPlexis' technology enables improved targeting of complex immunotherapy treatments to cancer patients. Predictive biomarker data on TCR Engineered T-cell, CAR-T cell, and Checkpoint Inhibitor based therapeutics to detect a multiplexed
range of functions from individual patient cells using proprietary bioinformatics will be discussed. These biomarkers indicate which patients will be responders and non-responders providing breakthrough insights for biopharma
and translational centers in highly urgent areas of oncology today.
10:15 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Pre-Clinical Models for the Evaluation of Novel Therapies and Anti-Tumor Immune Reponses
Marcus Bosenberg, M.D., Ph.D., Associate Professor of 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 cells lines that form
tumors following injection into immune competent C57Bl/6J mice. These models represent an ideal set of models for the study of cancer immunology and response to immune therapies.
11:30 Understanding the Biology and Clinical Translation of Syngeneic Mouse Models: What Do They Really Represent?
Elaine Hurt, Ph.D., Senior Scientist, MedImmune
Immune check-point inhibitors are changing the landscape of cancer patient care. While clinical efficacy is apparent, complete understanding of who benefits from IO therapy is still emerging. Preclinical models and the understanding
of when these models are predictive of patient responses are evolving as well. I will present the work that MedImmune has conducted to characterize syngeneic models to understand where these particular models fit into the preclinical
tool kit.
12:00 pm Preclinical Assessment of Combination of Erdafitinib and αPD-1 Antibody in FGFR2-Driven Genetically Engineered Mouse Model of Lung Cancer
Sangeetha Palakurthi, Ph.D., Head of Cancer Biology and
Pharmacology, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute
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. To test this hypothesis, we evaluated Erdafitinib in combination with αPD-1 antibody
in an autochthonous FGFR2K660N/p53 mutant GEMM of lung cancer, in which tumors develop within the context of an intact immune microenvironment. Tumor bearing FGFR2K660N/p53 mutant mice treated with Erdafitinib with or without
αPD-1 antibody showed significant tumor regressions compared to control and αPD-1 antibody monotherapy arms. We observed significant survival benefit in the combination group over Erdafitinib monotherapy. Further,
immune profiling and biomarker studies suggested that the survival benefit with combination treatment in FGFR-driven lung cancer GEMM may be driven through simultaneous mechanisms of blocking tumor intrinsic FGFR pathway enhancement
of anti-tumor immunity. Thus, data presented here provided a rationale for the combined clinical testing of JNJ-493 and PD-1 blockade in patients with FGFR-altered lung cancers.
12:30 Luncheon Presentation: Development of a Novel Phenotypic Platform for Therapy Selection and Understanding Biology of Tumor Immune Response
Pradip Majumder, CSO, Mitra Biotech
1:00 Session Break
1:30 Chairperson’s Remarks
Elaine Hurt, Ph.D., Senior Scientist, MedImmune
1:35 Co-Presentation: Translational Cancer Imaging for Drug Development and Precision Medicine
Quang-Dé Nguyen, Ph.D., Director, Lurie Family Imaging Center, Senior Scientist, Center for Biomedical Imaging in Oncology, Research Associate in Radiology, Harvard Medical School
Annick D. Van Den Abbeele, M.D., Associate Professor,
Radiology, Harvard Medical School; Chief, Department of Imaging, Dana-Farber Cancer Institute; Founding Director, Center for Biomedical Imaging in Oncology (CBIO), Imaging, Dana-Farber Cancer Institute
This presentation will discuss several important issues in translational imaging such as Imaging probe developments for immune-oncology applications, imaging co-clinical trials, bidirectional interactions between the mouse hospital
and the cancer center, interactions with pharmaceutical companies.
2:05 PANEL DISCUSSION: Mouse Models as a Driver for Translational Immuno-Oncology
Moderator: Elaine Hurt, Ph.D., Senior Scientist, MedImmune
Modelling toxicity
The tumour microenvironment
Immune competency (immunocompromised versus competent models)
Panelists: Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis Institute of Biomedical Research
Sangeetha Palakurthi, Ph.D., Head of Cancer Biology and Pharmacology, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute
Quang-Dé Nguyen, Ph.D., Director, Lurie Family Imaging Center, Senior Scientist, Center for Biomedical Imaging in Oncology, Research Associate in Radiology, Harvard Medical School
Annick D. Van Den Abbeele, M.D., Associate Professor, Radiology, Harvard Medical School; Chief, Department of Imaging, Dana-Farber Cancer Institute; Founding Director, Center for Biomedical Imaging in Oncology (CBIO), Imaging,
Dana-Farber Cancer Institute
2:35 Refreshment Break in the Exhibit Hall (Last Chance for Poster Viewing)
3:10 Chairperson’s Remarks
Ian McNiece, Ph.D., Executive Consultant, CellMed Consulting
3:20 Preclinical Tumor Models for Evaluating Bispecific Redirected T-Cell Therapeutics
Divya Mathur, Ph.D., Principal Scientist, Pfizer Oncology
Strong evidence exists supporting the important role T-cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. We have developed a bispecific protein
engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T cell populations via the CD3 complex in the presence
of solid tumors expressing target antigens.
3:50 Modeling for Preclinical Assessment of Treg Adoptive Therapy
Simrit Parmar, M.D., Assistant Professor, Department of Stem Cell Transplantation,
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Tregs are essential for immune homeostasis by maintaining peripheral tolerance and inhibiting autoimmune responses and pathogenic tissue damage. Adoptive therapy with Tregs has been shown to be safe and effective in diseases such
as graft vs. host disease, inflammatory bowel disease. The application of Treg adoptive therapy has tremendous promise to combat autoimmune diseases and inflammatory disorders.
4:20 Preclinical Tumor Models to Assess Efficacy of Cellular Immunotherapy Products that Include a Safety or Activation Molecular Switch
Eric Yvon, Ph.D., Director, CAR Program, Research and Development, Bellicum Pharmaceuticals,
Inc.
The CID technology platform was designed to address the challenges of current cellular immunotherapies by enabling control over cellular activities and functions. Our CID platform consists of molecular switches triggered inside
the patient by infusion of small molecule rimiducid. The “safety switch” is designed to lead to apoptosis, and the “activation switch” is designed to lead to activation and proliferation of immune cells.
4:50 Close of Conference
5:00 Symposia Registration