Cambridge Healthtech Institute’s 5th Annual

Immunomodulatory Approaches
( 免疫調節の手法 )

免疫反応の利用

2020年3月10日~11日

 

免疫調節の手法をテーマにしたこのカンファレンスプログラムでは、T細胞エフェクター、骨髄由来抑制細胞、二重特異性抗体のFc領域との結合などのトピックにスポットライトを当てながら、免疫細胞とサイトカインを活性化したり、抑制したりする方法について議論します。

Final Agenda

3月9日(月)

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.

3月10日(火)

7:30 Registration and Morning Coffee

自然免疫細胞の標的化

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, 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

Karagiannis_SophiaSophia 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 CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade, Bridging Innate and Adaptive Immunity

Fromm GeorgeGeorge 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.

ONCO-design-Biotechnology 9:40 Immunogenic Cell Death, a Novel Screening Platform Integrating Tumor Cells and Immune Cells Co-Culture Assays

Mirjolet_Jean-FrancoisJean-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-MorenoVictoria 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

Gruijl_TanjaTanja 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

二重特異性抗体と抗体薬物複合体の免疫調節

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

Neri_DarioDario 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

Beers_StephenStephen 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

Cragg_MarkMark 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 A Novel Half-Life Extended BiTE® Antibody Construct Targeting CD33/CD3 in AML

Kischel_RomanRoman 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

Codarri_LauraLaura 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

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

19:05 Close of Day

3月11日(水)

7:45 Registration and Morning Coffee

T細胞エンゲージング構築物

8:30 Chairperson’s Remarks

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

8:35 Next-Generation Bispecifics for Cancer Immunotherapy

Morrow__MichelleMichelle 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 EdwardsCarolyn 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

van_der_Vliet_Hans 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

Smith_Enell_Karin 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

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。