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)
14:05 Multiple Checkpoint Blockade with Bispecific Antibodies
John 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 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 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
16:30 Characterising the Early Response to Checkpoint Inhibition Immunotherapy in the CT26 Cancer Model
David 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 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 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
18:30 – 21:30 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
KEYNOTE SESSION
08:35 Investigations into Mechanisms of Immune Tumour Rejection
Dario 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 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
11:20 Tumour-Localised Costimulatory T-Cell Engagement by Bispecific CD137 (41BB) Agonists
Shane 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 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.
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
14:05 Novel Combination Immunotherapy Engaging with Myeloid Cells
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 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-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 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 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