Targeting the Tumour Microenvironment banner

- 肿瘤微小环境 -

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.

Final Agenda

MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING

Recommended Short Course*

SC3: Introduction to the Tumour Microenvironment and Response to Cancer Immunotherapy

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

APPROACHES TO TARGET THE TUMOUR STROMA

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

Christian Klein, PhD, Oncology Discovery & Translational Area, Cancer Immunotherapy Discovery, 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, ETH Zürich

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 Sponsored Presentation (Opportunity Available)

15:45 Networking Refreshment Break


PLENARY KEYNOTE SESSION

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

19:30 End of Day

TUESDAY 13 NOVEMBER

07:45 Registration and Morning Coffee

TARGETING MYELOID CELLS TO OVERCOME IMMUNO-SUPPRESSION

08:30 Chairperson’s Remarks

Len Seymour, PhD, Professor, Gene Therapies, Oncology, University of Oxford

08:35 Myeloid Cells in Tumor Microenvironment: Targeting Opportunities

Dmitry Gabrilovich, MD, PhD, Professor, Immunology, Microenvironment and Metastasis, The Wistar Institute

Myeloid-derived suppressor cells (MDSCs) are a population of myeloid cells generated in cancer. These cells represent a pathologic state of activation of monocytes and neutrophils, are characterized by a distinct set of genomic and biochemical features and can be distinguished by specific surface molecules. The salient feature of these cells is their ability to inhibit immune responses. These cells can be targeted therapeutically.

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

Marie H. Kosco-Vilbois, PhD, CSO, Novimmune SA

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

ANTAGONISTIC APPROACHES

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

IMPACT OF CHECKPOINT INHIBITORS

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 Development of Therapeutic Antibodies Targeting Suppressive Immune Cells in the Tumor Microenvironment to Boost Effector Cell Anti-Tumor Activity

Pascal Merchiers, PhD, Vice President, R&D, Tusk Therapeutics Ltd.

Tumors are masters in downregulating the immune response that aims at eliminating them. As such it is critical in immune therapy to target the negative suppressor cells driving the latter process. Tusk Therapeutics is developing antibodies that can effectively reduce the levels of these regulatory cells and enable the activation of effector cells. During this talk the preclinical proof-of-concept and development of these antibodies will be discussed.

15:50 Sponsored Presentation (Opportunity Available)

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing

ADVANCES IN THE CLINIC / IMPACT OF ONCOLYTIC VIRUSES AND VECTOR VACCINES ON IMMUNE MODULATION

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 of Oxford

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

* 活动内容有可能不事先告知作更动及调整。

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