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

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

TARGETING INNATE IMMUNE CELLS

8:30 Organizer’s Welcome Remarks

Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute

8:35 Chairperson’s Remarks

Sophia N. Karagiannis, BA, MS, PhD, Reader, Translational Cancer Immunology, St. John’s Institute of Dermatology, 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, Reader, Translational Cancer Immunology, St. John’s Institute of Dermatology, 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 Epigenetic Regulation of Myeloid-Derived Suppressor Cells by the CBP-Bromodomain

Jane Grogan, PhD, Head Adaptive Tumor Immunity & Principal Scientist, Cancer Immunology, Genentech

9:40 Sponsored Presentation (Opportunity Available)

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 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.

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 Session Break

IMMUNE MODULATING BISPECIFIC ANTIBODIES AND ADCs

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 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.

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 New Developments for BiTE® Antibody Constructs Targeting Cancer

Roman Kischel, MD, Director Research & Early Development Lead, Amgen Research Munich GmbH

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 Problem Solving Roundtable Discussions

18:05 Welcome Reception in the Exhibit Hall with Poster Viewing

19:05 Close of Day

WEDNESDAY 11 MARCH

7:45 Registration and Morning Coffee

T CELL-ENGAGING CONSTRUCTS

8:30 Chairperson’s Remarks

Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences, ETH Zürich

8:35 Lowering the Activation Threshold of Effector T Cells: A Novel Approach to Increase the Number of Patients Responding to Cancer Immune Therapy

Manfred Kraus, PhD, Director, In Vivo Pharmacology & Oncology, Pfizer

9:05 CB213: A Second-Generation Checkpoint Inhibitor Optimally Configured for Therapeutic Efficacy

James Legg, PhD, Senior Vice President, Research, 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 ATOR-1017, a 4-1BB Antibody Developed for Tumor-Directed Immunotherapy of Cancer

Karin Enell Smith, PhD, Senior Scientist, Preclinical Development, 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

PLENARY KEYNOTE SESSION

11:15 Organizer’s Remarks

Ngoc ‘Emily’ Le, PhD, Conference Producer, Cambridge Healthtech Institute

11:20 Chairperson’s Remarks

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine

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

Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme

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

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