Currently there is huge excitement about the tumour microenvironment. Investigators are discovering the many mechanisms used by the tumour to defend itself from immune attack from the host. These mechanisms are on the tumour surface and in the stromal
microenvironment. This track on Targeting the Tumour Microenvironment presents extraordinary findings that increase our understanding of cancer, and investigations to overcome these barriers. We will present promising results in vitro, in vivo and in the clinic.
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MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING
Recommended Short Course*
SC3: Introduction to the Tumour Microenvironment and Response to Cancer Immunotherapy - View Detailed Agenda
Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton
Frederick Arce Vargas, MD, PhD, MRCS, Group Leader, Translational Research, Autolus
The tumour microenvironment (TME) is a complex, dynamic environment in which extracellular matrix (ECM), soluble factors, immune cells, stromal cells and tumour cells interact. Each of these components is key to the establishment and growth of the
tumour, as well as impacting tumour cell behaviour and response to treatment. For example, stromal cells such as fibroblasts and macrophages display tumour promoting properties, driving proliferation and survival whilst propagating an immunosuppressive
environment. In this short course, we will discuss the nature of the TME, how the tumour promotes an immunosuppressive environment and what opportunities this presents for reversing immune suppression to deliver effective immunotherapy.
*Separate registration required.
MONDAY 12 NOVEMBER
12:00 Conference Registration (Foyer C)
13:30 Organizer’s Welcome
Nicole Lyscom, PhD, Senior Conference Director, Cambridge Healthtech Institute
13:35 Chairperson’s Opening Remarks
Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
13:45 Novel Approaches to Target the Tumor Stroma for Cancer Immunotherapy
Christina Claus, PhD, Senior Scientist, Oncology, Immunotherapy, pRED, Roche Innovation Center, Zurich
This presentation will examine the prevalence of FAP expression in tumors and the design of our FAP-IL2v and FAP-4-1BBL fusion proteins including the preclinical mechanism of action, and their application in combination therapy.
14:15 Impact of Cytokine Fusion Proteins Delivered to the Tumour Microenvironment
Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences,
Certain pro-inflammatory cytokines (e.g., IL2, IL12, TNF) can potently activate the immune system, but are often toxic at low doses, preventing escalation to therapeutically active regimens. The fusion of suitable cytokine payloads to tumor-homing
antibodies leads to a dramatic increase in therapeutic index. In this lecture, I will present preclinical and clinical results, obtained in collaboration with Philogen.
14:45 Selective IL-2 Immunotherapy to Fuel the Anti-Tumor Immune Response
Onur Boyman, MD, Professor and Chair, Immunology University Hospital
Zurich, University of Zurich
Following the impact of immune checkpoint inhibitors, novel immunotherapies are entering clinical testing in patients with advanced cancer, including interleukin-2 (IL-2)-based approaches. But what are the mechanisms of action, benefits, and differences
of IL-2-based immunotherapies in comparison to immune checkpoint inhibitors? This presentation will discuss these aspects of IL-2 immunotherapy by presenting data on selective and improved IL-2 formulations.
15:15 Abcam’s Custom Services Capabilities – from Development to Commercialization
Jamie Campbell, Head of Custom Services, Custom Manufacturing, Abcam
Abcam’s comprehensive approach to developing antibodies against challenging targets leverages three antibody discovery platforms: RabMAb®, NGS-based antibody discovery, and phage display, used in combination with comprehensive assay
cascades. We partner with biopharma and diagnostic companies to develop antibodies as key reagents in drug discovery, in vitro diagnostics and therapeutics.
15:30 Sponsored Presentation (Opportunity Available)
15:45 Networking Refreshment Break (Foyer D)
16:15 Moderator’s Opening Remarks
Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV
16:20 Bicycles and Bicycle Drug Conjugates
Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics
Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many
indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs), a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected
to enter clinical trial in Q1 2018.
17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ
Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich
Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently
developed a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic
proteins, produced and secreted by the infected cells.
18:20 Welcome Reception in the Exhibit Hall with Poster Viewing (Pavilion 1)
19:30 End of Day
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TUESDAY 13 NOVEMBER
07:45 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Len Seymour, PhD, Professor, Gene Therapies, Oncology, University of Oxford
08:35 Engineering, Efficacy and Functional Evaluation of a First In Class IgE Antibody for Cancer Therapy
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 could be an important determinant of clinical efficacy. Engineering anti-tumour antibodies with IgE class Fc regions may harness known properties of IgE that mediate immune clearance
of parasites. Anti-tumour IgE potentiated monocyte/macrophage recruitment and re-education against tumours. A first-in-class antibody has reached clinical testing in patients with solid tumours and may offer opportunities to extend the current
IgG-only class of monoclonal antibodies.
09:05 Manipulation of Myeloid Cells for Optimal Antibody Immunotherapy
Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group,
University of Southampton
Tumours are multicellular organs containing a plethora of host cell types. Amongst these, cells of the myeloid lineage are attracted and co-opted for tumour growth and survival – and critically, are altered to help deliver immune suppression.
In this presentation, I will detail the various stimuli that drive myeloid cell alterations in this microenvironment and discuss strategies to elicit their repolarization to augment antibody immunotherapy.
09:35 Breaking the Truce between Macrophages and Cancer in Order to Conquer Solid Tumors
Nicolas Fischer, PhD, Head, Research,
In the war on cancer, tumors exploit the immune checkpoint, CD47, to induce a truce with macrophages and even dendritic cells. To reinstate the anti-tumor capacity of innate and adaptive immunity, we target blockade of CD47 to the tumor, avoiding
collateral damage of healthy cells. Combining a blocking CD47 arm with an anti-mesothelin arm in a bispecific antibody reprograms these immune cells toward a proinflammatory activation state leading to effective killing of ovarian cancer cell
lines in vivo.
10:05 IgA as Novel Isotype to Treat Cancer, Enhancement by Targeting Neutrophil Checkpoint Inhibitors
Jeanette Leusen, PhD, Associate Professor, Translational
Immunology, University Medical Center Utrecht
This presentation will discuss the importance of neutrophils as a massive source of effector cells, and how they can be activated in the tumour environment. It will be demonstrated how antibodies of IgA isotype effectively engage myeloid effector
cells for cancer immunotherapy. Evidence that IgA antibodies result in a reduction in tumour size in mouse models will be presented together with preclinical evidence that IgA causes fewer side effects in the treatment of neuroblastoma.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
11:15 KEYNOTE PRESENTATION: TNFR2 Antagonism: It Doesn’t Get Any Better - A Treg and Oncogene Targeted Therapy
Denise L. Faustman, MD, PhD, Director, Immunobiology,
Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
Tumor necrosis factor receptor-2 (TNFR2) is a signaling molecule found on the surface of the most potent regulatory T-cells; signaling through TNFR2 proliferates cell through NF-kB. TNFR2 is also abundantly expressed on the surface of many
human tumors as on oncogene. We propose that blocking TNFR2 selectively targets abundant TNFR2+ tumor-infiltrating Tregs and directly kill TNFR2-expressing tumors. With multi-year efforts we have created TNFR2 antagonistic antibodies with
tumor microenvironment specificity.
11:45 A-TIGIT Antagonist Antibody EOS884448 Shows Dual Mechanism of Action by Restoration of T-Cell Effector Functions and Preferential Depletion of Treg
Gregory Driessens, PhD, Project Leader &
Head, in vivo Pharmacology, iTeos Therapeutics
TIGIT is a co-inhibitory receptor expressed by lymphoid populations. Antagonist anti-TIGIT antibodies have the potential to restore effector functions of T and NK cells by blocking TIGIT-ligand interaction and by depleting Treg that express
high TIGIT level. This presentation will focus on the clinical development of EOS884448 a new antagonist anti-TIGIT Ab that induces potent monotherapy antitumor activity through different mechanisms of action and offers strong therapeutic
potential in clinic.
12:15 Sponsored Presentation (Opportunity Available)
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:45 Dessert Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
14:15 Chairperson’s Remarks
Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, University of Southampton
14:20 Targeting Immune Checkpoints in Cancer: Mechanistic Insights
Frederick Arce Vargas, MD, PhD, MRCS, Group Leader, Translational Research, Autolus
Preclinical data in mouse models has suggested that the mechanism of action of antibodies targeting co-stimulatory and co-inhibitory molecules in T-cells might extend beyond engagement of blockade of these receptors, relying upon their additional
capacity to deplete regulatory T-cells through antibody-dependent cell-mediated cytotoxity. There is evidence that human Fc gamma receptors also mediate this mechanism in the case of anti-CTLA-4 and anti-CD25 antibodies. This evidence
supports the importance of understanding the immune landscape in the tumour microenvironment for the design of the next generation of immune regulatory antibodies.
14:50 Broad Impact of anti-PD-LI on the Tumour Microenvironment
Yan Qu, PhD, Senior Principal Scientist, Rinat Pfizer
15:20 Targeted Delivery of Endosomal Toll-Like Receptor Agonists to the Tumour Microenvironment for the Promotion of Anti-Tumour Immunity
Diana Corogeanu, Scientist, Biotherapeutics, NIBSC (National Institute for Biological Standards and Control)
Endosomal toll-like receptor (TLR) agonists have been shown to promote anti-tumour immune responses when administered to the tumour site. However, systemic administration has shown limited clinical efficiency and dose-dependent immune-mediated
adverse effects. We are exploring targeted delivery of endosomal TLR agonists to the tumour microenvironment by attaching them to tumour-homing antibodies used in cancer therapy. This presentation will discuss methods of biochemical
conjugation, but also complex formation with a cationic peptide fusion antibody, and their respective advantages and caveats.
15:50 Sponsored Presentation (Opportunity Available)
16:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
17:00 Clinical Advances with Entinostat HDAC Inhibitors in Metastatic Breast Cancer
Michael L. Meyers, MD, PhD, CMO, Syndax Pharmaceuticals, Inc.
17:30 Studies with the Oncolytic Virus VSV-GP, Cancer Vaccines and Immune-Modulation: The Yin and the Yang
Philipp Mueller, PhD, Principal Scientist, Cancer
Immunology & Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG
The talk will provide a short introduction to the MoA of oncolytic virotherapies, selective replication of the oncolytic virus VSV-GP in tumor cells, tumor cell lysis and reshaping of the tumor microenvironment. It will further outline
the effectiveness of VSV-GP as an IO enabler in the poorly “T-cell inflamed” tumour space for a broad range of cancers and highlight VSV-GP as a non-mutagenic virus, which can be armed with transgenes and synergizes with
other (non)-IO therapies.
18:00 Targeting Immunotherapy to the Tumour Microenvironment Using Bispecific Antibodies
Len Seymour, PhD, Professor, Gene Therapies, Oncology, University
Oncolytic viruses replicate selectively within cancer cells and kill them, amplifying themselves selectively within tumour tissue. They can be ‘armed’ to produce specific biologics (such as bispecific T-cell engager antibodies,
BiTEs) and secrete them into the tumour microenvironment, where the BiTEs can activate endogenous T-cells to kill chosen target cells. This paper will discuss using BiTEs that target tumour cells and also tumour-associated fibroblasts
for reversal of tumour-related immunosuppression
18:30 End of Targeting the Tumour Microenvironment
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