Cambridge Healthtech Institute’s Inaugural
Preclinical and Translational Immuno-Oncology
Advanced Models of Immuno-Oncology and Preclinical Strategies in Preparation for Clinical Trials
21-22 March 2019
Modelling the immune system and its response to cancer sets a particularly difficult challenge. The different cell types required, heterogeneity of tumours and the signaling pathways involved mean that multiple advanced models are required to justify
clinical trials. But which ones do you choose? At the Preclinical and Translational Immuno-Oncology conference, we will delve deeper into the advantages and disadvantages of each model and the strategies employed to help translate
positive results to clinical trials. Models to be discussed include humanized mice models, syngeneic and xenograph models, 3D models and organoids, plus many more.
Final Agenda
THURSDAY 21 MARCH
12:15 Registration
12:45 Dessert Break in the Exhibit Hall with Poster Viewing
14:00 Chairperson’s Opening Remarks
Catarina Brito, PhD, Lab Head, Animal Cell Technology Unit, iBET
14:05 FEATURED PRESENTATION: Sharpening Preclinical Insight to Improve Clinical Relevance
Sara Colombetti, PhD, Head of Oncology Discovery Pharmacology, Research and Early Development (pRED), Roche Pharma
Preclinical mouse models are key tools to evaluate the activity of cancer immunotherapies. They are instrumental to understand the mechanism of action of tested compounds, and help identifying rationale combination partners for best anti-tumor efficacy.
We show here how the Pharmacology Group at the Roche Innovation Center Zurich has been developing over the past years cutting edge mouse models platform with improved clinical relevance and predictive value.
14:35 3D-3-Culture: A Tool to Unveil Macrophage Plasticity in Tumor Microenvironment
Catarina Brito, PhD, Lab Head, Animal Cell Technology Unit, iBET
We have been exploring culture strategies based on alginate microencapsulation and stirred culture systems to develop tools to study macrophage plasticity in response to therapy. In 3D-3-cultures (co-culture of tumor cell spheroids, fibroblasts and monocytes),
immunosuppressive features of cancer microenvironment are recapitulated, with infiltration of macrophages in the tumor mass and trans-polarization into M2-like phenotypes. Challenging of the system with therapeutic compounds induced modulation of
the M2-like phenotype.
15:05 Somatically Engineered Preclinical Models for Immunotherapy Studies
Danilo Maddalo, PhD, Lab Head, Oncology, Novartis
Generation of animal models with a fully functional immune system is key for the study and the development of treatments targeting the tumour microenvironment. The implementation of genome editing technologies such as the CRISPR/Cas9 system has revolutionized
the field of disease modeling as it allows the precise induction of specific oncogenic signatures in somatic cells of a specific organ. In this talk, a short overview of the current and future applications of in vivo somatic genome editing will be presented.
15:35 Novel I-O Drug Discoveries Empowered by Humanized Animal Models
Yi (Benny) Yang,
Director, Antibody Research and Development Division, Biocytogen
In vivo efficacy evaluation has always been a rate-limiting step during therapeutic antibody discovery due to species specificity. Using gene-editing technology, we have generated and functionally validated a series of single and double humanized
mouse models for the I/O field such as B-hPD-1/hPD-L1, B-CTLA-4, B-hOX-40, B-hCD47/h-SIRPa and B-hCD3e. These models are very useful not only for single agent treatment, but also for combination therapy and bispecific antibody development.
16:05 Networking Refreshment Break
16:30 Therapeutic Combination Benefits of IDO1 Inhibition with T Cell Activation Approaches in Preclinical Models
Manfred Kraus, PhD, Director In Vivo Pharmacology & Oncology, In Vivo Pharmacology & Oncology, Pfizer
Tumors use IDO1 as a major mechanism to induce an immunosuppressive microenvironment. IDO1 is induced in response to inflammatory stimuli such as IFNγ and promotes immune tolerance by depleting tryptophan and producing tryptophan catabolites, including
kynurenine, in the tumor microenvironment. This leads to effector T-cell anergy and enhanced Treg function. As a nexus for the induction of key immunosuppressive mechanisms, IDO1 represents an important immunotherapeutic target in oncology. In pre-clinical
models EOS200271/PF-06840003, a novel selective IDO1 inhibitor, reduced intratumoral kynurenine levels by over 80% and inhibited tumor growth both in monotherapy and in combination with antibodies modulating immune checkpoints.
17:00 NEW: Advanced Humanized Mouse Models to Investigate the Mechanisms of Immunotherapy
Adriano Flora, PhD, Senior Manager, The Jackson Laboratory
17:30 Targeting TNFR Family Members: Challenges and Opportunities
Jane Willoughby, Senior Post-Doc, Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton
Costimulation above simple TCR engagement is required for full and sustained activation of T cells leading to effective anti-tumour responses. TNF receptors mediate a number of costimulatory functions and can be activated using monoclonal antibodies.
However, the rules of engagement for these receptors is not yet clear with careful dissection of their mechanisms of action still required. Our current understanding of these various aspects will be discussed.
18:00 Close of Day
Dinner Short Course Registration
Recommended Dinner Short Course*
18:30 - 21:30
SC3: Managing the Challenges of Bioassays for Immuno-Oncology - Detailed Agenda
*Separate registration required
FRIDAY 22 MARCH
8:00 Morning Coffee
8:30 Chairperson’s Remarks
Mahendra Deonarain, BSc, PhD, CEO and CSO, Antikor Biopharma
8:35 Rational Design to Combine with Checkpoint Immunotherapy
Siu Tim Cheung, PhD, Associate Professor, Surgery, The Chinese University of Hong Kong
Majority of the studies have shown the interaction of PD-L1/PD1 between tumor cells and T-lymphocytes with unclear involvement of other immune components. Natural killer (NK) cells have been progressively used in the treatment of hematologic malignancy
with unclear efficacy in solid tumors. The present study will discuss the role of PD-L1/PD1 targeting on NK cell-mediated cytotoxic function.
9:05 Regulatory Challenges in Immuno-Oncology
Andrew Exley, PhD, Medical Assessor, Biologicals and Biotechnology Unit, Medicines and Healthcare Products Regulatory Agency (MHRA)
This presentation will cover: rapid development of novel therapies challenging regulators and innovators in Immuno-Oncology; symbiosis between regulators and innovators supported by frequent interaction; accelerated programmes through the MHRA/EMA/FDA/SMC
providing opportunities for early patient access; surrogate outcome measures and limited data sets presenting particular challenges; pseudoprogression and tail effects presenting opportunities and challenges to regulators and innovators.
9:35 Immunogenicity Assessment for Immuno-Oncology Programs
Margot El-Khouri,
PhD, Immunology Sales Specialist, Sales, ProImmune Ltd.
Whether immunogenicity is desired as for cancer epitopes or unwanted in the context of later drug development safety, immunogenicity assessment is critical for every step of anticancer therapy development. As the market leader in the field, ProImmune
has developed expert, standardised, consistent in-house assays which provide a deep understanding of antigenicity of epitopes and whole compounds. We will describe our capabilities using selected case studies placed in the context of epitope identification
and immunogenicity assessment.
10:05 Problem Solving Roundtable Discussion
How Can We Leverage Cutting Edge in vivo Preclinical Models for Cancer Immunotherapy Profiling?
Sara Colombetti, PhD, Head of Oncology Discovery Pharmacology, Research and Early Development (pRED), Roche Pharma
Human vs Mouse Experiments in the Era of Immuno-Oncology
Danilo Maddalo, PhD, Lab Head, Oncology, Novartis
11:00 Networking Coffee Break
11:20 Glyco-Optimization of Antibodies Targeting Immune Checkpoint Molecules: Case Studies of an Agonist and an Antagonist
Timo Lischke, PhD, Scientist, Preclinical Pharmacology & Cancer Immunology, Glycotope GmbH
Glyco-engineering is an established strategy to enhance ADCC activity of tumor antigen-targeting antibodies, e.g. anti-CD20 or anti-EGFR. In two case studies of an agonistic anti-CD40 and an antagonistic anti-PD-L1 antibody, we show using different
functional assays (e.g. ADCC, MLR, DC maturation, T cell activation) that glyco-optimization can also be applied to enhance activity of antibodies targeting immune checkpoint molecules.
11:50 Targeting a Novel Immune Escape Axis for the Treatment of Cancer
Eugene Zhukovsky, PhD, Senior Scientific Director of Immuno-Oncology, Research, Oxford Biotherapeutics
Evasion of the host’s immune system by tumor cells is a well-established mechanism of tumor establishment and progression. Using proteomic analysis of membrane-associated proteins from whole tumors, tumor infiltrating lymphocytes (TIL), and
activated/exhausted T-cell models, we have identified a receptor-ligand axis involved in an active immune escape mechanism. We have generated an antibody targeting this axis with potential therapeutic benefit.
12:20 T Cell Dysfunction and Combination Immunotherapy
Dimitris Skokos, PhD, Associate Director, Immunology & Inflammation, Regeneron Pharmaceuticals
Immune checkpoint inhibitor therapies bolster the antitumor activity of CD8+ T lymphocytes. We used single-cell analysis of tumor-infiltrating lymphocytes to probe the mechanisms responsible for the synergy of PD-1 blocking and GITR agonist antibodies
in enhancing tumor control in mouse cancer models. This combination immunotherapy resulted in a synergistic increase in memory precursor effector T cells that depended on availability of specific costimulatory pathways. These results provide a
mechanistic rationale for conducting further clinical trials of combined anti-GITR and anti-PD-1 immunotherapy in human cancer.
12:50 Networking Refreshment Break with Light Snack
13:30 Chairperson’s Remarks
Dimitris Skokos, PhD, Associate Director, Immunology & Inflammation, Regeneron Pharmaceuticals
13:35 Antigen Discovery for Development of Personalized Cancer Immunotherapy
Michal Bassani-Sternberg, PhD, Head of Immunopeptidomics Lab, Oncology, University Hospital of Lausanne and the Ludwig Institute for Cancer Research, Lausanne
The remarkable clinical efficacy of the immune checkpoint blockade therapies has motivated researchers to discover immunogenic epitopes and exploit them for personalized therapies. We have shown that analysis of tissue-derived immunopeptidome by mass
spectrometry (MS) facilitates identification of neoantigens that are the leading targets for T-cell recognition of cancer cells. Training ligand predictors on MS-based refined binding motifs significantly improves the prediction of clinically
relevant neoantigens for personalized anti-cancer vaccines.
14:05 Antibody Fragment Drug Conjugates (FDCs) - Application in Solid Tumours
Mahendra Deonarain, BSc, PhD, CEO and CSO, Antikor Biopharma
Alternative strategies to antibody drug conjugates (ADCs) are emerging to tackle the issues of solid tumour penetration and payload-related adverse effects. Antikor’s approach is to use recombinant antibody fragments to generate antibody fragment
drug conjugates (FDCs) that potentially open up the therapeutic window. Progress on our FDC for gastric cancer will be presented.
14:35 Getting Under The Hood - Mass Cytometric Analysis of CAR Mechanisms
Jonathan Fisher, BSc, BM, MClinRes, MRCPCH, PhD, Clinical Postdoctoral Fellow, Cancer Section, UCL Institute
of Child Health
Despite the benefits of chimeric antigen receptor (CAR)-T cell therapies against lymphoid malignancies, efforts to limit T-cell exhaustion and off-tumour toxicity have been blunted by a lack of mechanistic understanding. We demonstrate how time-course
mass cytometry facilitates rapid assessment and diagnosis of problems in CAR design. We introduce a novel construct, which combines properties of innate-like gdT cells with chimeric costimulatory receptors to target AML without on-target off-tumour
toxicity.
15:05 Novel Platforms and Antibody-Based Strategies for Detection of Tumour-Causing Agents and Tumours
Richard O’Kennedy, PhD, Vice-President for Research Development and Innovation, Qatar Foundation
This lecture will examine how different antibody-based approaches and associated platforms, including sensors, can be used to detect tumours and tumour-causing agents. It will describe how highly specific antibodies can be generated and customized
for particular analyses and platforms. Use of antibody profiling for the detection of colorectal cancer and the production and use of antibodies to detect cancer-associated toxins, including mycotoxins and microcystins, will be outlined.
15:35 End of Summit