Immuno Oncology Europe
Immuno Oncology Europe

Immunomodulatory Approaches track banner

 

Immunomodulatory Approaches track banner

 

The success of immune checkpoint blockade with CTLA-4 and PD-1 and developments with agonists and cytokines have paved the way for further research, particularly approaches for cancers unresponsive to known agents, and for advanced methodologies that enhance the activity of cancer-attacking cells. This track presents developments with a range of checkpoint blockers, separately, in combination, and together as part of bispecifics. In addition, it focuses on the roles and control of lymphocytes, NK cells and macrophages, and examines agonistic approaches, and developments with cytokine therapeutics.

Final Agenda

Tuesday, 21 March

13:00 Conference Registration

14:00 Chairperson’s Opening Remarks

Catherine Sabatos-Peyton, Ph.D., Senior Investigator II, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)

CHECKPOINT INHIBITORS AND MODES OF ACTION

14:05 Multiple Checkpoint Blockade with Bispecific Antibodies

John_DesjarlaisJohn Desjarlais, Ph.D., CSO, Xencor, Inc.

We have optimised an Fc-containing bispecific antibody platform with high stability, efficient production, and antibody-like pharmacokinetics. We will present application of the platform to dual checkpoint blockade bispecifics for T-cell activation. We show that a PD1 x CTLA4 bispecific antibody enhances T-cell activation relative to anti-PD1 alone and comparably to a combination of anti-CTLA4 and anti-PD1 antibodies. Additional checkpoint combinations also display promising preclinical activity.

14:35 Application of the DART Platform to Enhance Checkpoint Blockade

Paul_MoorePaul Moore, Ph.D., Vice President, Cell Biology and Immunity, Macrogenics, Inc.

The flexibility afforded by the DART platform for creation of bispecific antibodies incorporating desired targeting specificities or binding valencies, lends itself to a range of therapeutic applications. As example, the functional characterisation of MGD013, a DART molecule designed to simultaneously block PD-1 and LAG-3, non-redundant checkpoint pathways leveraged by tumours to evade immune surveillance, will be presented. Additional strategies to enhance anti-tumour immune responses using the DART platform will also be shared.

15:05 Understanding the Immune Landscape and Fc Receptors in the Tumour Microenvironment for Engineering of Immune Modulatory Antibodies

Sergio_QuezadaSergio A. Quezada, Ph.D., Professorial Research Fellow, Research Department of Haematology, University College London Cancer Institute

It has been demonstrated in the pre-clinical setting that the activity of certain immune modulatory antibodies extends beyond simple receptor stimulation or blockade, relying on an additional capacity to deplete Treg by antibody dependent cell-mediated cytotoxicity (ADCC). Translation of this into the clinic depends on understanding the immune landscape of immune modulatory antibody targets and of the Fc receptors in the tumour microenvironment. We have evaluated this in in vivo models and tested the effects of antibody engineering in the anti-tumour immune response. 

 

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

PD-1 and PD-L1: MECHANISMS OF RESPONSE, NON-RESPONDERS, AND PERSONALISED APPROACHES

16:30 Characterising the Early Response to Checkpoint Inhibition Immunotherapy in the CT26 Cancer Model

David_ProssorDavid Prossor, MMedSci, Tumour Immunology & Experimental Oncology, CRUK, University of Southampton and Southampton General Hospital

Cytotoxic T lymphocytes (CTLs) eliminate neoplastic cells; however, tumours are able to evade the immune response. Interestingly, Treg depletion in the CT26 mouse tumour model revealed the emergence of potent anti-tumour CTLs, highlighting the importance of priming. In addition, checkpoint inhibition immunotherapy induces protective anti-tumour responses in ~30% of mice. Tumour cells were detected in draining lymph nodes of challenged mice. Anti-PD1 treated mice showed a more diverse T-cell receptor (TCR) repertoire than the control group. These findings suggest tumours restrict TCR repertoires and that immunotherapy acts to broaden the TCR composition to enhance antitumour potency.

17:00 Immunomodulatory Approaches Beyond PD-1

Andrea_van_ElsasAndrea van Elsas, Ph.D., CSO, Aduro Biotech Europe

T cell checkpoint inhibitors set a clinical paradigm providing significant benefit to patients diagnosed with advanced cancer. Despite success, the majority of patients do not respond to PD-1, PD-L1 or CTLA-4 blockade. Raising the number of patients benefiting from cancer immunotherapy requires novel therapeutic approaches aimed at these non-responders, for instance using novel immunomodulatory antibodies and combination with active immunization.

17:30 Adapting a 3D Microfluidic Culture System to Study Immune Checkpoint Blockade for Personalised Immunotherapy

Amir_ArefAmir R. Aref, Ph.D., Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School

Immunotherapy with PD-1 blockade can provide prolonged and durable responses for patients with metastatic melanoma, but only in a limited number of patients. We have successfully adapted a novel microfluidic cell culture technology that recapitulates the tumour microenvironment (TME) by incorporating a model extracellular matrix (ECM), and allowing controlled analysis of growth factor and cytokine-mediated effects. Improved understanding of the response to immune checkpoint inhibitors within the tumour microenvironment will facilitate future efforts to screen for compounds that enhance the response to immune checkpoint blockade, and may ultimately provide a platform for the ‘personalization’ of immunotherapy.

18:00 End of Day One of Immunomodulatory Approaches

18:00 Dinner Short Course Registration

18:3021:30 SC1: New Directions in Cancer Immunotherapy or SC2: CAR T and TCR Manufacturing Challenges to Anticipate and Overcome

Separate registration required.

Wednesday, 22 March

08:30 Chairperson’s Remarks

Nicolai Wagtmann, Ph.D., Executive Vice President and CSO, Innate Pharma

CURRENT UNDERSTANDING OF THE ROLE OF THE IMMUNE SYSTEM IN CANCER

KEYNOTE SESSION

08:35 Investigations into Mechanisms of Immune Tumour Rejection

Dario_NeriDario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zurich

Certain immunotherapy approaches (e.g., immunological check-point inhibitors, bispecific antibodies, antibody-cytokine fusion proteins) have the potential to eradicate cancer and to confer protective anticancer immunity. Recently, advances in MHC class-I peptidome analysis and multiplex tetramer technology have enabled characterisation of the process of tumour cell recognition by T cells at the molecular level. In this lecture, I will present preclinical and clinical data, outlining how certain tumours are rejected as a consequence of immunotherapeutic interventions.

09:05 Immuno-Oncology: Current and Future Advances

Robert_WilkinsonRobert W. Wilkinson, Ph.D., Director, Oncology Research, MedImmune Ltd.

Immuno-oncology (IO) therapies, such as checkpoint inhibitors (e.g. anti-CTLA-4 and anti-PD-1/PD-L1 antibodies) are demonstrating significant promise in the treatment of haematological and solid cancers. However some patients fail to respond, it is believed that the lack of activity in these patients is limited by insufficient immune priming and or by immunosuppression, within the tumour microenvironment. Further advances to the IO field are taking the form of novel immunotherapies aimed at targeting: T-cell effector responses (such as, TNFRSF agonists); antigen presenting cell function (such as, TLR agonists and virotherapy); and the elimination of immune suppression pathways.


09:35 Problem Solving Roundtable Discussions

Table 1: Challenges with Targeting Immune Checkpoint Inhibitors

John Desjarlais, Ph.D., CSO, Xencor, Inc.

Table 2: Pros and Cons of Immunocytokine-Based Immunotherapeutics

Dario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zurich

Table 3: Stimulation of Agonistic Pathways for Antibody-Based Cancer Immunotherapy

Moderator: Shane Olwill, Ph.D., VP, Development, and Head, Immuno-Oncology, Pieris Pharmaceuticals, Inc.

Table 4: Targeting the Innate Immune Response

Catherine Sabatos-Peyton, Ph.D., Senior Investigator II, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)

Table 5: Enhancing Fc Receptor Effector Function in Cancer

Stephen Beers, Ph.D., Associate Professor, Cancer Sciences Unit, Faculty of Medicine, University of Southampton

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

AGONISTIC RECEPTOR ENGAGEMENT AND IMMUNOSTIMULATORY APPROACHES

11:20 Tumour-Localised Costimulatory T-Cell Engagement by Bispecific CD137 (41BB) Agonists

Shane_OlwillShane Olwill, Ph.D., VP, Development, and Head, Immuno-Oncology, Pieris Pharmaceuticals, Inc.

 We used the Anticalin platform to generate the CD137 bispecifics PRS-343 (CD137/HER2) and PRS-342 (CD137/GPC3). In ex vivo assays we could show that T cells are efficiently activated when incubated with bispecifics and tumour-target-positive cells. T-cell activation is tumour target-dependent and heavily influenced by geometry of the bispecific. We will present in vivo proof of concept data utilizing a humanised mouse model as well as data on drug-like properties of the bispecifics.

11:50 Multivalent Nanobodies for Development of Differentiated Immuno-Oncology Therapeutics

Catelijne_StortelersCatelijne Stortelers, Ph.D., Senior Project Leader, Technology, Discovery, Ablynx NV

An overview of Ablynx's Nanobody platform technology and advantages in the development of bi-and multi-specific Nanobody drugs for immune checkpoint modulation will be presented, including the selection of Nanobodies to either the same target or to different targets for generating formats with additional or synergistic activity. This presentation will cover a multivalent approach for an agonistic Nanobody against the co-stimulatory immune checkpoint receptor GITR. 

IntelliCyt_Sartorius 12:20 Advancing the Discovery of Immunotherapeutics with Large Scale, Multiplexed Experiments on Cells and Proteins of Immune System
Peter Djali, Ph.D., European Sales Director, IntelliCyt Corporation

12:35 Enjoy Lunch on Your Own

14:00 Chairperson’s Remarks

Stephen Beers, Ph.D., Associate Professor, Cancer Sciences Unit, Faculty of Medicine, University of Southampton

 

ACTIVATING THE INNATE IMMUNE SYSTEM: NK CELLS AND MYELOID CELLS 

14:05 Novel Combination Immunotherapy Engaging with Myeloid Cells

Wei_Xu Wei Xu, M.D., Ph.D., Senior Scientist, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich

I will discuss the rationale and data supporting the selected use of immunotherapeutic combinations that are modulating the innate myeloid cells in preclinical models of cancer. Further I will discuss the novel discovery of biomarkers in clinical trials with immune checkpoint inhibition.

14:35 TTI-621 (SIRPaFc): An Innate Immune System Checkpoint Inhibitor Targeting the CD47 “Do Not Eat” Signal

Bob_UgerBob Uger, Ph.D., CSO, Trillium Therapeutics, Inc.

TTI-621 is a soluble SIRPα-Fc fusion protein designed to block CD47, a “do not eat” signal that suppresses macrophage phagocytosis. There is strong evidence that many tumours express high levels of CD47 to escape macrophage-mediated immune surveillance and thus CD47 has recently emerged as a promising target in immune-oncology. The preclinical rationale and emerging clinical data for this novel innate immune system checkpoint inhibitor will be discussed.

15:05 TIM-3: Beyond T-Cell Checkpoints

Catherine_Sabatos-PeytonCatherine Sabatos-Peyton, Ph.D., Senior Investigator II, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)

TIM-3 was initially described as a co-inhibitory receptor expressed on IFN-gamma-secreting T cells, now broadly understood to be part of the class of “checkpoint proteins.” However, in addition to its role on dysfunctional T cells, TIM-3 is broadly expressed on cells of the innate immune system, including myeloid cells and NK cells. Emerging evidence supports a critical inhibitory role for TIM-3 on myeloid populations, and that blockade of TIM-3 on myeloid cells can support an anti-tumour immune response.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

16:00 Development of Antibodies to KIR Checkpoint Receptors on NK Cells

Nicolai_WagtmannNicolai Wagtmann, Ph.D., Executive Vice President and CSO, Innate Pharma

NK cells play important roles in control of cancer by directly killing target cells and by secreting cytokines and chemokines that stimulate T cells. These NK cell activities are controlled by activating and inhibitory NK cell surface receptors, which recognise ligands on target cells. The talk will describe the rationale and early development of lirilumab, a first-in-class therapeutic antibody designed to block KIR checkpoint receptors on NK cells.

16:30 Innate Immune Agonists Can Overcome a Suppressive Tumour Microenvironment to Repolarise Tumour-Associated Macrophages and Augment Antibody Therapy

Stephen_BeersStephen Beers, Ph.D., Associate Professor, Cancer Sciences Unit, Faculty of Medicine, University of Southampton

Tumour-associated macrophages (TAM) typically are poorly cytotoxic and contribute to immune suppression making treatments less effective. We assessed a panel of innate immune agonists for their ability to re-polarise macrophages into a state optimal for mAb-mediated immunotherapy. Reagents which were able to overcome immunosuppression in the tumour microenvironment effectively reversed the TAM inhibitory FcγR profile and provided strong adjuvant effects to anti-CD20 mAb in murine models of normal and malignant B cell depletion.

17:00 Close of Immunomodulatory Approaches

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