2017 Archived Content
The selection of appropriate preclinical models based on similarity to human biology and disease genotype and phenotype carries considerable potential to ensure higher predictability of preclinical trials. The design and interpretation of first-in-man
trials remains a major challenge in the development of novel anticancer agents. Key study design elements such as schedule, escalation strategy, targeted patient population, etc. rely heavily on preclinical (usually in vivo) data. This situation
brings into question the predictability of preclinical tumor models as well as the method of analysis and translation of the results of preclinical studies. It is especially difficult to model for preclinical assessment of cancer immunotherapy, the
most actively developing area in oncology. The need for stimulating the response of the immune system adds to the complexity of preclinical models and the applications. Cambridge Healthtech Institute’s Preclinical Models for Cancer Immunotherapy and Combinations conference aims to bring together cancer researchers and clinicians in order to initiate knowledge and opinion exchange around preclinical tumor models, including immunocompetent models, and the strategies for preclinical design and assessment of
cancer immunotherapy and combination therapy.
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Final Agenda
Day 1 | Day 2 | Speaker Biographies | Download Brochure
Wednesday 15 November
7:00 Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
Sara Brett, Ph.D., Director Translational Sciences , GSK
8:30 Characterization of the Tumor Micro Environment in Model Systems to Guide Clinical Biomarkers of Response
Sara Brett, Ph.D., Director Translational Sciences , GSK
Varieties of model systems are used in immuno-oncology to define biomarkers of response or resistance in response to therapy. These evaluations are typically made in various immune rich compartments, such as the tumor microenvironment or peripheral blood.
We will discuss observations from multiple such model systems with the strengths and caveats of each to meaningfully project biomarker strategies for clinical development.
9:00 Strategic Approaches to Enhance Sensitivity to Checkpoint Blockade
Brian B. Haines, Ph.D., Principal Scientist, Pharmacology, MSD
Immunotherapeutic strategies, such as CTLA-4 and PD-1 blockade, have revolutionized the treatment of many types of cancer, providing significant benefit to patients. However, not all patients or cancer types respond to single agent therapies.This talk
will provide a bench to bedside and back approach to combination strategies that enhance both the breadth and the depth of response to checkpoint blockade.
9:30 Discovery of Novel Resistance Mechanisms to HDM2/p53 Inhibitors by Insertional Mutagenesis in Mice
Michael Rugaard Jensen, Ph.D., Director, Head of ONC Discovery Pharmacology Basel, Novartis
Institutes for BioMedical Research
The novel p53/MDM2 inhibitor HDM201 is currently in clinical trials. We used piggyBac transposon insertional mutagenesis to discover resistance mechanisms occurring during treatment with HDM201. Comparison of tumors with acquired resistance to HDM201
and untreated tumors identified genes that were differentially targeted by piggyBac transposons. Resistant tumors displayed a complex clonality pattern suggesting emergence of several resistant subclones. Our findings identify mechanisms by which
p53 wild-type tumors escape MDM2-targeted therapy.
10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Humanized Mouse Models as Relevant Tools for in vivo Profiling of Cancer Immunotherapies
Sara Colombetti, Ph.D., Head of Oncology Discovery Pharmacology, Roche Innovation
Center Zürich
Humanized mouse models have recently attracted more attention in the field of cancer immunotherapy. We will present how our preclinical research group at the Roche Innovation Center Zurich, part of the pRED Oncology Discovery organization, has been developing
and investigating this model as a relevant and unique tool for in vivo profiling of cancer immunotherapies.
11:15 Infection and Immune Control of Human Oncogenic Gamma-Herpes Viruses in vivo
Christian Münz, Ph.D., Co-Director of the Institute of Experimental Immunology,
University of Zürich
Whole genome sequencing between mouse and man has identified reproduction, olfaction and the immune system as the three organs of maximal diversity. In the case of the immune system, this difference has most likely evolved through challenges by pathogen
infections, which are particular to the ecological niche that the human species occupies. Most of these pathogens do not infect mice. Thus, the functional capacity of the human immune system can probably be best studied in the context of infections
that have challenged it during its evolution.
11:45 PDX
Models in Humanized Mice: Novel Approaches to Test Anti-Cancer Therapies
Thomas Metz, Ph.D., Head of Business Operations, Charles River
The extensive molecular characterization of PDX models allowed the pre-selection of target-relevant models and enabled even more focused approaches. The advent of immunotherapy brought about a need for immune-competent pre-clinical tumor models. PDX models
in humanized mice combine the advantages of both systems and enable the preclinical characterization of immunotherapies alone and in combination with conventional anticancer agents.
12:15 Enjoy Lunch on Your Own
12:45 Session Break
13:45 Chairperson’s Remarks
Brian B. Haines, Ph.D., Principal Scientist, Pharmacology, MSD
13:50 PANEL DISCUSSION: Mouse Models as a Driver for Translational Immuno-Oncology
Brian B. Haines, Ph.D., Principal Scientist, Pharmacology, MSD
- Modeling resistance
- Modeling toxicity
- The tumour microenvironment
- Immune competency (immunocompromised versus competent models)
14:50 Refreshment Break in the Exhibit Hall with Poster Viewing
15:30 The Use of Preclinical Models to Uncover New Combination Opportunities in Cancer Treatment
Martin Aichinger, Ph.D., Lab Head, Pharmacology and Translational Research Oncology, Boehringer
Ingelheim
Combinations of cancer cell targeted and immune modulatory drugs are becoming more relevant in emerging combination therapies in cancer. Since many of the cancer-targeted drugs also have an impact on the immune system, a better understanding of these
mechanisms allows the design of new and smarter combination strategies. Relevant preclinical models and a case story on the different mode of actions of Smac mimetics, which resulted in a rational combination approach, will be discussed.
16:00 Evaluation of Multi-Therapeutic Approaches Combining Cancer Chemo-Immunotherapy, Caloric Restriction Mimetics (Crms) and Immune Checkpoint Inhibitors against Murine Tumor Models
Jonathan Pol, Ph.D., Postdoctural Researcher, Kroemer Lab, Cordeliers Research Center, INSERM
Caloric restriction during chemotherapy is associated with enhanced anticancer efficacy in mice. We identified compounds, referred as caloric restriction mimetics (CRMs), which mimic the biochemical and functional effects of caloric restriction. When
combined to chemo-immunotherapies, CRMs improved treatment efficacy against several engrafted and induced murine tumor models. Adding immune checkpoint inhibitors resulted in a remarkable enhancement of antitumor activity. Based on these promising
findings, clinical investigation of such multi-therapy is encouraged.
16:30 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.
Topic: Preclinical Design of Combination Cancer Therapy
Moderator: Michael Rugaard Jensen, Ph.D., Director, Head of ONC Discovery, Pharmacology Basel, Novartis Institutes for BioMedical Research
- Understanding the intersection of critical signaling pathways
- Combining without eroding therapeutic index
- Overcoming tumor heterogeneity
- Translatability to the clinic
Topic: Targeting Cancer with Genome Editing
Moderator: Danilo Maddalo, Ph.D., Lab Head, ONC Pharmacology, Novartis Institutes for BioMedical Research, Novartis Pharma AG
- CRISPR/Cas9 models: advantages and disadvantages
- Where did the CRISPR/Cas9 did not hold his promises
- Future applications of CRISPR/Cas9 in mouse modeling
Topic: Organoid Models and Next Generation Drug Development
Moderator: Anita Seshire, Ph.D., Lab Head Cellular Pharmacology, Translational Innovation Platform Oncology, Merck KGaA
- Proving genetic and phenotypic stability
- Benefits for preclinical testing and drug screening
- Implications for personalized medicine
17:30 Welcome Reception in the Exhibit Hall with Poster Viewing
18:30 Close of Day and Dinner Short Course Registration
19:00 Recommended Dinner Short Course*
(SC2) Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy
*Separate registration required
Day 1 | Day 2 | Speaker Biographies | Download Brochure
Thursday 16 November
8:00 Registration and Morning Coffee
8:25 Chairperson’s Remarks
Danilo Maddalo, Ph.D., Lab Head, ONC Pharmacology, Novartis Institutes for BioMedical Research, Novartis Pharma AG
8:30 CRISPR/Cas9 in Preclinical and Drug Discovery
Danilo Maddalo, Ph.D., 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.
9:00 Modelling and Targeting Pancreatic Cancer and Its Microenvironment by Genome Engineering and Gene Editing in Mice
Dieter Saur, Professor of Molecular Biology, Technical University of Munich
Maintenance and drug resistance of pancreatic cancer (PDAC) depends on cancer cell intrinsic mechanisms and a stroma that is immunosuppressive and supports tumour growth. We generated novel models for PDAC subtypes that permit spatial and temporal
control of gene expression. These tools provide unparalleled access to the native biology of PDAC and its hosting stroma, and rigorous genetic validation of candidate therapeutic targets in autochthonous tumours and the immune system.
9:30 POSTER PRESENTATION: Immunology Insight from 3D Microfluidic Models: The Role of Monocytes in TCR-Redirected T Cell Immunotherapy
Sharon Wei Ling Lee, PhD Student, Singapore MIT Alliance for Research & Technology
9:45 POSTER PRESENTATION: A New 3D Model of Human Lung Cancer to Investigate the Correlation of Epithelial-to-Mesenchymal Transition, Invasion and Drug-Resistance
Claudia Goettlich, PhD Candidate, Fraunhofer Institute for Silicate Research
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Multicellular 3D Models for Preclinical Drug Discovery
Anita Seshire, Ph.D., Lab Head Cellular Pharmacology, Translational Innovation
Platform Oncology, Merck KGaA
Primary cell cultures from patient material were established and grown in 3D-assays. Multicellular 3D spheres contained either monocytes or fibroblasts and the role of trophic cells on stemness and microenvironmental factors was studied. We
were able to enrich for tumor-initiating cells, which were transplanted into mice. Tumor formation was enhanced when CSC were enriched in spheres prior to transplantion. The addition of monocytes and fibroblasts enhanced stemness and generated
a tumor-specific phenotype of plated monocytes.
11:15 A Predictive in vitro Preclinical Package to Assess Safety and Efficacy of Cancer Immunotherapy
María José Oliva Martín, Ph.D., Senior
Scientist, Immunocore Ltd.
ImmTAC molecules are bispecific pico-molar affinity TCR-based biologics that recognise peptides presented by Class I MHC on the surface of target cells, thus offering a unique advantage over current antibody therapies. Such peptides are typically
human specific, and therefore traditional in vivo models are unsuitable for safety assessments. Here we present how Immunocore’s in vitro preclinical package has approached
this challenge and the incorporation of CRISPR technology to assess specificity.
11:45 Assessing Efficacy of Cancer Immuno- and Combination Therapy in Co-Cultures of Patient-Derived Microtumors and Immune Cells
Christian Schmees, Ph.D., Head of Tumor Biology, Molecular Biology
Department, NMI Natural and Medical Sciences Institute at the University of Tübingen
Recently we have been developing a co-culture platform comprising patient tumor tissue-derived microtumors to evaluate the impact of immunotherapeutic treatment with regard to kinetics of infiltration and cytotoxic killing by autologous immune
cells. I will present data from efficacy testing of targeted therapeutics, checkpoint inhibitors and their combinations in different tumor types.
12:15 Luncheon
Presentation: CANscript™: A Phenotypic-Based, Tumor Modeling Platform for Drug Discovery and Development
Mark Paris, Ph.D., Associate Director, Translational Applications, Mitra Biotech
We have developed and validated an ex-vivo platform technology (CANscript™) using patient material (tumor, autologous ligands and immune cells) to predict anti-tumor efficacy in the clinic across several drug classes. Data suggests
this technology can be used to understand MOA in I-O along with indication scouting, combination testing and general de-risking of cytotoxic, targeted and IO clinical programs. Supporting evidence will be presented.
Day 1 | Day 2 | Speaker Biographies | Download Brochure