Cambridge Healthtech Institute’s 5th Annual
Immunomodulatory Approaches
Harnessing the Immune Response
10-11 March 2020
With an abundance of immunotherapies and increasing biomarker availability, there are ever more choices for oncologists looking to employ the immune system in their treatment plans. The tumour microenvironment, and all its heterogeneity, represents a
huge challenge in stratifying patient populations and selecting immunomodulatory therapies. At the 5th Annual Immunomodulatory Approaches conference we will discuss how immune cells and cytokines can be activated or suppressed to
elicit a desired treatment response with a focus on T cell effectors, myeloid-derived suppressor cells and bispecific antibody Fc engagement.
Final Agenda
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MONDAY 9 MARCH
Recommended Short Course*
SC2: Next-Generation Immunotherapies - LEARN MORE
Stephen Beers, PhD, Professor, Immunology and Immunotherapy, Cancer Immunology, University of Southampton Faculty of Medicine
Eric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals
Dario Neri, PhD, Professor, Biomacromolecules, Swiss Federal Institute of Technology (ETH Zürich), Switzerland
John Maher, MD, PhD, Consultant and Senior Lecturer, Immunology, Cancer Studies, King’s College London
Sophia N. Karagiannis, BA, MS, PhD, Professor, Translational Cancer Immunology and Immunotherapy, St. John’s Institute of Dermatology, Basic & Medical Biosciences, King’s College London
*Separate registration required.
TUESDAY 10 MARCH
7:30 Registration and Morning Coffee
8:30 Organizer’s Welcome Remarks
Nicole Lyscom, PhD, Senior Conference Director, Cambridge Healthtech Institute
8:35 Chairperson’s Remarks
Sophia N. Karagiannis, BA, MS, PhD, Professor, Translational Cancer Immunology and Immunotherapy, School of Basic & Medical Biosciences, King’s College London
8:40 Re-Activating Macrophages in the Tumour Microenvironment with Anti-Tumour IgE Antibodies
Sophia N. Karagiannis, BA, MS, PhD, Professor, Translational Cancer Immunology and Immunotherapy, School of Basic & Medical Biosciences, King’s College London
Fc region engineering to enhance antibody effector functions may improve clinical efficacy. We generated anti-tumour antibodies with IgE class Fc regions. We demonstrated that IgE can kill tumours by harnessing known immunological mechanisms it naturally
employs in parasite clearance. IgE potentiated monocyte/macrophage recruitment and re-education of alternatively-activated to classically-activated anti-tumour phenotypes. A first-in-class IgE is in clinical testing in oncology, offering opportunities
to extend the current IgG-only class of therapeutics.
9:10 Attend Concurrent Track
CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade, Bridging Innate and Adaptive Immunity
George Fromm, PhD, Vice President of Research and Development, Shattuck Labs, Inc.
The CD47/SIRPa axis has recently been validated as an exciting clinical target, and importantly, its blockade could enhance antigen cross-presentation in the setting of immune-neglected (anti-PD1 refractory) tumors. The subset of dendritic cells which
are the most potent antigen cross-presenters express CD40, and its stimulation enhances CD8+ lymphocyte activation by these cells. SIRPa-Fc-CD40L can simultaneously block immunosuppressive signals and activate innate immune cells; inducing a potent
anti-tumor adaptive immune response.
9:40 Immunogenic Cell Death, a Novel Screening Platform Integrating Tumor Cells and Immune Cells Co-Culture Assays
Jean-François Mirjolet, PhD, Head, In Vitro Sciences Department, Oncodesign
Using our in-house developed screening strategy (platform with four assays including co-culture assays), we have identified and characterized several Immunological Cell Death (ICD) inducers and a Nanocyclix compound for the three key damage-associated
molecular patterns (secreted ATP, HMGB1 release and surface calreticulin) and cell viability in several cell lines. Evaluation of dendritic cell phagocytosis and cytokine secretion levels showed that ICD activates both innate and adaptive arms of
the immune system.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 The Actomyosin Cytoskeleton of Cancer Cells Regulates Macrophage Function and Therapy Responses
Victoria Sanz-Moreno, PhD, Professor, Cancer Cell Biology, Bart’s Cancer Institute, Queen Mary University
The lab works on understanding how the cytoskeleton in cancer cells promotes tumour growth and dissemination. The lab combines 'OMICs', state of the art microscopy in 3D matrices, molecular biology, animal models and digital pathology in patient tissues
to identify molecular determinants that correlate with cancer progression, metastatic potential and therapy response. Furthermore, we aim to define how the cytoskeleton in cancer cells controls the immune microenvironment.
11:20 FEATURED PRESENTATION: Turning Neutrophils into Potent Tumour Killers with IgA
Jeanette Leusen, PhD, Associate Professor and Head Immunotherapy Group, Translational Immunology, University Medical Centre Utrecht
IgA is a strong activator of neutrophils to kill cancer cells. CD47 is a ‘don’t eat me’ signal for cancer cells and healthy cells, that binds to SIRPalpha on neutrophils as an inhibitory receptor or an innate checkpoint molecule.
CD47 can be manipulated to not bind to SIRPalpha anymore, and this strongly enhances the IgA anti-tumor effect in vitro and in vivo.
11:50 Dendritic Cell Targeted Immune Modulation in Melanoma**
Tanja de Gruijl, PhD, Professor and Chair of Translational Tumor Immunology, Medical Oncology, VU University Medical Center Amsterdam
In melanoma, hampered DC development in the microenvironment of tumors and their draining lymph nodes facilitates immune escape. We have explored targeted interventions to counteract this suppression, resulting in the design of an oncolytic adenovirus,
counteracting DC-suppressive signalling pathways in the melanoma microenvironment, and the local administration of CpG-B as a means to bolster DC activation in the sentinel lymph node and prolong recurrence-free survival of early-stage melanoma
patients.
12:20 Luncheon Presentation (Sponsorship Opportunity Available)
12:50 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing
13:20 Chairperson’s Remarks
Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences, ETH Zürich
13:25 Antibody-Cytokine Fusions: From Discovery to Phase III Clinical Trials
Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences, ETH Zürich
Antibodies can be used as delivery vehicles for cytokine payloads, with the aim to generate a pro-inflammatory environment at the tumor site. In this lecture, I will present preclinical and clinical results on antibody-cytokine fusions, with a
main emphasis on interleukin-2, interleukin-12 and tumor necrosis factor as therapeutic payloads.
13:55 Optimising STING Agonists for Cancer Therapy
Stephen A. Beers, PhD, Professor of Immunology and Immunotherapy, Centre for Cancer Immunology, Cancer
Sciences Unit, University of Southampton
Largely, patients with immunologically ‘cold’ tumours do not respond to immune checkpoint blockade. The intracellular DNA sensing system, stimulator of interferon genes (STING), is an ideal candidate pathway to target as an adjuvant
to cancer immunotherapy. Here we will explore how STING agonism can be used to ‘heat up’ tumours, how this can be self-limiting and discuss ways to maximize its efficacy for combination immunotherapy.
14:25 Optimising Agonistic Immunostimulatory Antibodies for Cancer Immunotherapy
Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton
Agonistic antibodies directed to immunostimulatory receptors are a currently untapped source for immunotherapy. Whereas checkpoint blockers have translated into the clinic, the rules for agonistic antibodies have been more difficult to discern
and these reagents await further optimisation. Here we discuss the salient properties of antibodies required to strongly agonise these receptors and discuss potential strategies for the future.
14:55 Sponsored Presentation (Opportunity Available)
15:25 Refreshment Break in the Exhibit Hall with Poster Viewing
16:05 Attend Concurrent Track
A Novel Half-Life Extended BiTE® Antibody Construct Targeting CD33/CD3 in AML
Roman Kischel, MD, Director Research & Early Development Lead, Amgen Research Munich GmbH
BiTE® antibody constructs are recombinant bispecific antibodies that efficiently recruit host T-cells for redirected killing of cancer cells expressing a selected target antigen. AMG 673, a CD33/CD3 specific BiTE® antibody construct, has
been extensively characterized preclinically. Initial data from a first-in-human phase 1 dose escalation study evaluating AMG 673 in patients with R/R AML will be discussed.
16:35 Novel Immune-Cell Targeted IL2v to Deliver IL-2R Signaling to Tumor Reactive T Cells via PD-1 whilst Blocking the PD-1 Pathway**
Laura Codarri Deak, PhD, Principal Scientist, Cancer Immunotherapy, Roche Pharmaceutical Research and Early Development
Interleukin-2 has been the first effective cancer immunotherapy to treat metastatic melanoma and renal cell carcinoma, although only a fraction of patients benefits, the anti-tumor responses are complete and durable. Unfortunately, IL-2 is toxic
and detrimentally expands regulatory T cells.
17:05 PANEL DISCUSSION: Means of Activating the Tumour Microenvironment
Moderator: Sophia N. Karagiannis, BA, MS, PhD, Professor, Translational Cancer Immunology and Immunotherapy, St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
Panellists: Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton
Panellist 2 to be Announced
Panellist 3 to be Announced
- Blockade mechanisms to consider
- How to engineer therapeutics to overcome blockade
- Sequestering immune cells and therapeutics to the tumour.
- Potential role of gamma delta
18:05 Welcome Reception in the Exhibit Hall with Poster Viewing
19:05 Close of Day
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WEDNESDAY 11 MARCH
7:45 Registration and Morning Coffee
8:30 Chairperson’s Remarks
Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences, ETH Zürich
8:35 Next-Generation Bispecifics for Cancer Immunotherapy
Michelle Morrow, PhD, Vice President, Preclinical Translational Pharmacology, F-star
The use of bispecific antibodies can potentially modulate anti-tumour immune responses. Bispecific antibodies: an attractive alternative to cancer treatment combinations. F-star’s approach to create bispecific mAb². In vitro and in
vivo efficacy of F-star bispecific antibodies targeting oncology pathways observed in preclinical studies.
9:05 CB213: A Second-Generation Checkpoint Inhibitor Optimally Configured for Therapeutic Efficacy
Carolyn Edwards, PhD, Principal Scientist, Translational Biology, Crescendo Biologics
CB213 is an asymmetric half-life extended Humabody product inhibiting the checkpoints PD-1 and LAG3. The talk will describe the approach taken to select an asymmetric molecule on the basis of optimal target engagement and activity using the modular
Humabody VH domain format. Preclinical characterization will be described, including in vitro function in patient derived T cells. Together these data support progression of CB213 into preclinical development.
9:35 Bispecific Gamma Delta T Cell Engagers for Cancer Immunotherapy**
Hans van der Vliet, MD, PhD, CSO, LAVA Therapeutics; Medical Oncologist, Amsterdam UMC
Vγ9Vδ2 T cells constitute the largest γδ T cell subset in human peripheral blood and are powerful anti-tumor immune effector cells that can be identified in many different tumor types. This presentation will discuss bispecific
antibodies designed to engage Vγ9Vδ2 T cells and their use for cancer immunotherapy.
10:05 NEW: ATOR-1017, a 4-1BB Antibody Developed for Tumor-Directed Immunotherapy of Cancer
Anne Månsson Kvarnhammar, PhD, Senior Scientist, Alligator Bioscience AB
ATOR-1017 induces a potent tumor-directed immune response, leading to an efficient tumor eradication and immunological memory in preclinical models. ATOR-1017 is FcγR crosslinking dependent, which is anticipated to direct immune activation
to the tumor where 4-1BB and FcγRs are highly expressed and reduce the risk for systemic immune activation, due to the high concentration of endogenous circulating IgG. A first-in-human Phase I study with ATOR-1017 is planned for 2019.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Solutions-Focused Speed Networking in the Exhibit Hall
11:15 Organizer’s Remarks
Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute
11:20 NEW: Chairperson’s Remarks
Reno Debets, PhD, Professor, Laboratory of Tumor Immunology, PI, Medical Oncology, Erasmus MC-Cancer Institute
11:30 Strategies to Improve Antitumor Efficacy of Genetically Engineered T Cells**
Stanley Riddell, MD, Scientific Director, Clinical Research, Fred Hutchinson Cancer Research Center; Professor, University of Washington
School of Medicine
Immune cells can be readily genetically modified to express natural tumor targeting antigen receptors or synthetic chimeric antigen receptors (CARs) that activate immune cell signaling pathways to result in destruction of tumor cells expressing
the relevant target molecule. The presentation will discuss advances in our understanding of receptor signaling and the development of strategies that combine therapeutic agents to improve efficacy and safely extend the spectrum of cancers
that can be treated with cell therapies.
12:00 PD-1 Antibodies Are Transforming Cancer Treatment
Kandeepan Ganeshalingam, MD, Executive Director,Therapeutic Area Head Oncology, European Clinical
Development Global Clinical Development, MRL, Merck Sharp & Dohme (MSD)
PD-1 antibodies have shown significant activity as monotherapy across multiple cancer types and lines of therapy. Precision medicine tools have been used to identify subjects most likely to respond to PD-1 antibody monotherapy, to provide
insight to potential resistance mechanisms, and to inform combination therapies. A number of these combinations have demonstrated significant activity in additional tumor types and lines of therapy.
12:30 Close of Immunomodulatory Approaches
**Presentations delivered via a live, interactive video conferencing platform.**
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