For successful Combination Immunotherapy, a better understanding is required of what is going on in the tumour, how the tumour antigens change, factors limiting the activity of T cells, and what the tumour is doing to provide an inhibitory
environment. The industry and academia are reaping the benefits of this knowledge and developing new combination approaches with new modes of action. In this track, attendees will discover how investigators are improving on the limitations of
monotherapies with the application of clever combination strategies.
Final Agenda
Tuesday, 20 March
13:30 Registration
14:00 Chairperson’s Opening Remarks
David Szymkowski, PhD, Senior Research Director, Biotherapeutics, Xencor, Inc.
14:05 KEYNOTE: Anti-Tumor Antibody Effector Contributions to Synergistic Innate and Adaptive Immunity
K. Dane Wittrup, PhD, Carbon P. Dubbs Professor, Chemical Engineering and Biological Engineering, Massachusetts Institute of Technology
There is a mounting body of evidence that therapeutic monoclonal antibodies (mAbs) against tumor-associated antigens (TAAs) are capable of profoundly synergizing with T cell-directed immunotherapies such as checkpoint blockade and adoptive cell
therapy. Two key components account for this synergy: (i) a self-vaccinal effect mediated by dendritic cells (DCs); and (ii) an inflammatory repolarization of the tumor microenvironment. Efficient exploitation of these mechanisms has tremendous
therapeutic potential.
14:35 Maximising the Therapeutic Potential of Immuno-Oncology through Novel Combinations
Robert W. Wilkinson, PhD, Director, Oncology Research, MedImmune Ltd.
Significant advances have taken place in our understanding of the interplay between cancer and the immune system, and intervention points for Immuno-Oncology (IO) therapies. The talk will review the current status of IO combinatorial approaches
and future areas of therapeutic advancement.
15:05 Advancing
Next-Gen IO Therapies from Research to the Clinic: 1. HTP Bispecifics & 2. Biomarker ID Using Machine Learning
Maria Wendt, PhD, Head, Science, Genedata
We present two aspects of our work: First, we address the need for more extensive exploration of the design space for bi/multi-targeting by automating the production and screening of very large panels of such candidate molecules. Second, we
apply machine learning methods to high-throughput NGS and multi-omic data to more rapidly advance these candidates in the clinic by simultaneously facilitating molecule evaluation and identifying the patient population most likely to benefit.
15:35 Refreshment break in the Exhibit Hall with Poster Viewing
16:15 Bispecific Antibodies for Dual Immune Checkpoint Inhibition
David Szymkowski, PhD, Senior Research Director, Biotherapeutics, Xencor, Inc.
Combinations of checkpoint-blocking antibodies are more efficacious than single inhibitors, but also cause greater immune-related toxicities. We reasoned that a bispecific antibody against two checkpoints would selectively target tumor-infiltrating
lymphocytes, improving safety and efficacy. We generated several dual-checkpoint inhibitors including XmAb20717 (anti-PD1 x anti-CTLA4) that are more efficacious in vivo relative to combinations of monospecific
checkpoint blockers, suggesting that such bispecifics may have clinical advantages over combination therapy for the treatment of cancer.
16:45 Optimizing Dual Checkpoint Blockade through Bispecific Molecules: From Concept to Clinic
Paul Moore, PhD, Vice President, Cell Biology and Immunology, Macrogenics, Inc.
MGD013, a bispecific PD1 x LAG3 targeting DART® molecule designed to antagonize two non-redundant inhibitory checkpoint pathways exploited by tumors to evade immune surveillance, has recently entered clinical study. The presentation
will cover the rationale for dual targeting of PD-1 and LAG-3, the synergistic biology achieved by MGD013 beyond that observed by mAb combinations, and additional preclinical studies to support IND filing and an overview of the
clinical study design.
17:15 Dual Targeting of PD-L1 and TA-MUC1 in Combination with Fc-Glycoengineering as a Novel Approach
to Overcome Current Limitations of Anti-PD-L1 Therapy
Johanna Rühmann, PhD, Senior Director, Internal Project Strategy & Cooperations, Glycotope GmbH
PM-PDL-GEX is a trifunctional antibody with binding sites for TA-MUC1 and PD-L1 and a functional Fc-part. By its rational construct design, the advantages of two highly effective targeting strategies are combined with respect to amplification
of anti-tumor modes of action and accumulation within the tumor. The results from our in vitro proof-of-concept study further underline the potential of Fc glycol-optimization to enhance not only cytotoxic
but also immunomodulatory antibody effector functions.
17:45 End of Day
18:00 Dinner Short Course Registration*
18:30 - 21:30 SC1: T-Cell Therapies: Current Field, Challenges and Future Directions
*Separate registration required.
Wednesday, 21 March
08:00 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Robert W. Wilkinson, PhD, Director, Oncology Research, MedImmune Ltd.
08:35 Targeting Immune Regulation at the Tumour Site
Sergio A. Quezada, PhD, Professorial Research Fellow, Research Department of Haematology, UCL Cancer Institute
In recent years, a number of publications have demonstrated the essential role that the tumour microenvironment and Fc receptors play for the in vivo activity of checkpoint targeting antibodies. In this
talk we will discuss novel development in this area relating the mechanism of action and the development of immune modulatory antibodies and combinations that promote intra-tumoural Treg with maximal modulatory activity.
09:05 Selective Targeting of Tregs in the Tumor Microenvironment
Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
Tregs are highly enriched in the tumor microenvironment and they are considered among the greatest barriers to successful immunotherapy because of their ability to powerfully inhibit the body’s antitumor immune response
when recruited or induced by growing tumors. Non-selective approaches to targeting Tregs have resulted in autoimmune side effects common to checkpoint inhibitors. New research suggests methods for selectively targeting
the Tregs unique to the tumor response as monotherapy and in combination with checkpoint inhibitors.
09:35 Problem Solving Roundtable Breakout Discussions
Table 1: Novel Combination Approaches for Immuno-Oncology
Moderator: Christian Klein, PhD, Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
Table 2: Challenges with Checkpoint Inhibitors in the Clinic
Moderator: Paul Moore, PhD, Vice President, Cell Biology and Immunology, Macrogenics, Inc.
Table 3: Evaluation of Rational Combinations for Immuno-Oncology
Moderator: Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
Table 4: Biological, Pre-Analytical and Analytical Variables that Impact Biomarker Data
Moderator to be decided
Table 5: Challenges with Targeting Immune Checkpoint Inhibitors
Moderator: David Szymkowski, PhD, Senior Research Director, Biotherapeutics, Xencor, Inc.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 RNA-Modified T Cells as a Tool to Deliver Immunomodulatory Agents to Brain Tumours
Fernanda Pohl-Guimaraes, Neurosurgery, University of Florida Gainesville
11:45 Enhancing Antibody Tumour Targeting with CD27 Agonists
Sean Lim, MB, ChB, PhD, Associate Professor and Honorary Consultant, Haematological Oncology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton>
Monoclonal antibodies can kill tumours by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T-cell responses. Here, we explore the therapeutic potential of
combining direct tumour-targeting antibodies with immunomodulating antibodies, with particular emphasis on the use of agonistic antibodies against the TNFR superfamily member, CD27. A detailed mechanistic analysis
on how anti- CD27 enhances direct tumour-targeting antibodies will be presented.
12:15 Getting
Closer to the Picture and Data for Immuno-Oncology Assays Using the Celigo Image Cytometer
Scott Cribbes, PhD, Director, Applications and Emerging Technologies, Nexcelom Biosciences LLC
Immuno-oncology assays are conducted by release assays, but can be inaccurate due to indirect supernatant measurement. We demonstrated the detection of antibody/cell-mediated cytotoxicity in 2D/3D models using the
Celigo. The image cytometer could analyze live cells to measure time/dose-dependent cytotoxicity. The proposed method can perform high-throughput cancer drug screening.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:15 Session Break
13:30 Dessert Break in the Exhibit Hall with Poster Viewing
14:00 Chairperson’s Remarks
Sean Lim, MB, ChB, PhD, Associate Professor and Honorary Consultant, Haematological Oncology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton
14:05 Novel Combination Approaches for Cancer Immunotherapy
Christian Klein, PhD, Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
This presentation will cover the experience with T cell bispecific antibodies, checkpoint inhibitors and immunomodulators as well as novel approaches to enhance their activity by combination therapy
14:35 Rational Combination Strategies to Augment Activity
of CD3 Bispecific Antibodies
Teemu Junttila, PhD, Senior Scientist, Translational Oncology, Genentech, Inc.
CD3 bispecific antibodies induce rapid activation of T cells leading to degranulation of cytolytic vesicles and apoptosis of target expressing cancer cells. Both CD8 and CD4 cells can kill tumor
cells in vitro although with distinct kinetics. T cell activation results also in feedback inhibition. PD1 up regulation has been described with multiple molecules
and shown to inhibit activity of CD3 bispecific antibodies. The role of other co-inhibitory molecules is less clear. Our goal is to systematically characterize the induction and functional
role of key co-inhibitory and co-stimulatory molecules upon treatment with CD3 bispecific antibodies to identify optimal combination strategies.
15:05 Targeting Immune Checkpoints with Bispecific Antibodies
John Haurum, PhD, CEO, F-star Biotechnology Ltd.
Combining immunotherapies for cancer treatment has shown numerous benefits over single agent. An attractive alternative is the development of bispecific antibodies that not only address two
pharmacological targets but may also result in novel biological mechanisms that are impossible to attain with combinations. This presentation will discuss the in vitro and in vivo efficacy of bispecifics targeting immune checkpoints commonly used by cancer to evade the immune system.
15:35 Facilitate Your Antibody Drug Discovery, from Lead Generation to Lead Optimization
LiuSong Yin, PhD, Vice Director, Department of Antibody, GenScript
Therapeutic antibody drugs have recently experienced explosive growth. In this talk, we will discuss cutting edge high throughput screening platforms for lead generation and examine characterization
technologies required for rational selection of lead therapeutic antibody drug candidates. We will also review current platforms for lead optimization, including humanization, developability
assessment and antibody affinity maturation. Join this interactive presentation to discuss more about therapeutic lead generation, lead characterization and lead optimization.
16:05 Refreshment Break in the Exhibit Hall with Poster Viewing
16:35 Promoting Host Anti-Tumor Immune Responses with
Targeted Protein Therapeutics
Gregory P. Adams, PhD, CSO, Eleven Biotherapeutics
Targeted Protein Therapeutics (TPTs) are fusion proteins comprised of tumor-targeting antibody fragments and cytotoxic protein payloads. The ability of TPTs to directly kill tumor cells via
a mechanism known as immunogenic cell death which stimulates host anti-tumor immune responses, thereby setting the stage for combination therapy with immune-oncology agents will
be discussed.
17:05 Hafnium Oxide Nanoparticles and Radiotherapy
to Convert Immunologically “Cold” Tumor into “Hot” Tumor
Sébastien Paris, PhD, Head, Biology, Non-Clinical, Discovery, Nanobiotix
Hafnium oxide nanoparticles (HfO2-NP) were designed to efficiently absorb ionizing radiation from within the tumor cells and augment dose deposition into the tumor. Preclinical studies have
shown superior potential of HfO2-NPs exposed to radiotherapy to trigger immunogenic cell death when compared to radiotherapy. In vivo cancer models in immunocompetent
mice have shown that radiotherapy-activated HfO2-NPs trigger immunogenic conversion of the tumor microenvironment while this effect is not observed with radiotherapy alone.
17:35 Towards Targeting the Tie2–αvβ3
Integrin Axis as a Novel Therapy for Angiogenesis
Niv Papo, PhD, Group Leader, Biotechnology Engineering, Ben Gurion University of the Negev
Emerging evidence has implicated increased activity of the receptor tyrosine kinase, Tie2, in the promotion of pathological angiogenesis. This activity is mediated mainly through the
downstream angiopoietin (Ang)-1 and Ang2-dependent Tie2 activation of integrins, rendering the Ang/Tie2/integrins axis an attractive putative target for cancer therapeutics. To engineer
inhibitors that target this axis, we developed novel single domain, non-immunoglobilin high affinity bispecific protein inhibitors against both Tie2 and α
vβ3 integrin.
18:05 Close of Combination Immunotherapy