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Track 1 Immuno-Oncology

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Monday, 14 March

07:30 Registration and Morning Coffee

08:30 Chairperson’s Opening Remarks

Robert Williams, Ph.D., Chief Drug Development Scientist, Cancer Research UK Centre for Drug Development

08:40 CARS and "Armoured" CARS

Renier BrentjensRenier Brentjens, Ph.D., Director, Cellular Therapeutics Centre, Memorial Sloan Kettering Cancer Center

T cells may be genetically modified to express chimeric antigen receptors (CAR) targeted to antigens expressed by tumor cells. We have developed this technology in the laboratory and translated this adoptive T cell approach in the clinic. Treatment of patients with CD19 targeted CAR T cells has resulted in remarkable remission rates in relapsed B cell acute lymphoblastic leukemia (B-ALL). We will present novel data on a next generation of CAR T cells, termed “armoured CARs” further genetically designed to overcome an immune suppressive tumor microenvironment through further genetic modification of CAR T cells. Promising preclinical studies utilizing these “armoured CAR” T cell approaches and their role in future clinical trials will be discussed.


AGONISTIC APPROACHES

09:10 Preclinical Development of the Human CD40 Agonistic Antibody ADC-1013

Peter Ellmark, Ph.D., Principal Scientist, Alligator Bioscience

Increasing the response rate while minimising toxicity can be achieved by directing the immune activation to the tumour. Alligator Bioscience currently evaluates intratumoural administration of a CD40 agonistic antibody (ADC-1013) in the clinic. The mode of action of ADC-1013, as well as the anti-tumour effects of combinations with other immune modulating antibodies have been evaluated in hCD40 transgenic mice in multiple syngeneic tumour models.

09:40 Preclinical Evaluation of an Anti-ICOS Agonist Antibody

Jennifer MichaelsonJennifer Michaelson, Ph.D., Director, Research, Tumour Biology, Jounce Therapeutics

Jounce is developing an agonistic antibody to the co-stimulatory molecule ICOS (Inducible CO-Stimulator molecule). Preclinical studies demonstrate that anti-ICOS antibodies are efficacious in syngeneic tumour models, with enhanced efficacy observed in combination with PD-1 inhibition. Mechanistic studies demonstrate agonistic effects of the antibody on T effector cells as well as preferential reduction of T regulatory cells. Together these data provide the rationale for development of a candidate antibody to be evaluated in the clinic in monotherapy and combination therapy settings. The lead anti-ICOS antibody is currently in IND-enabling studies.

Intellicyt10:10 Rapidly Screening a Novel Affinity Scaffold Library for PD-L1 Inhibitors Using the iQue Platform

Johnson_MattMatt Johnson, Ph.D., CTO, Avacta Life Sciences

Affimers are small stable antibody mimetics used as research and diagnostic reagents. High throughput protein expression and the capability of the iQue Screener allowed us to move through phage display, candidate expression and primary repertoire screening within 8 weeks of acquiring the target. We identified multiple clones that inhibit PD-L1/PD1 interaction enabling further investigation of these as biotherapeutics leads.

10:25 Tumor-Localized Costimulatory T-cell Engagement by Bispecific CD137 Agonists PRS-343 (CD137/HER2) and PRS-342 (CD137/GPC3)

Andrea Allersdorfer, Senior Group Leader, Protein Analytics, Pieris Pharmaceuticals, Inc.

We have generated CD137-targeting bispecifics designed to promote CD137 clustering by bridging CD137-positive T cells with HER2- or GPC3-positive tumor cells, thereby providing a potent costimulatory signal to tumor antigen-specific T cells. Data supporting the mode of action and favorable drug like properties of PRS-343 and PRS-342 will be presented.

10:40 Coffee Break with Exhibit and Poster Viewing


ADDITIONAL IMMUNOSTIMULATORY APPROACHES

11:20 Role of Isotype in Immunomodulatory Antibody Function

Ann White, Ph.D., Senior Research Fellow, Faculty of Medicine, Cancer Sciences Unit, University of Southampton

Monoclonal antibodies (mAb) that stimulate the immune system are revolutionising cancer treatment, delivering durable responses in previously untreatable disease. However, not all patients and tumours respond and toxicity can be problematic. In this talk I will review recent data examining the role of mAb isotype and Fc GAMMA receptor interaction in dictating mAb activity and discuss ways to optimise immunostimulatory agents through mAb engineering.

11:50 Hexavalent TNFR-Superfamily Agonists for Cancer Treatment and Immune Modulation: TRAIL, CD27L, CD40L and Beyond

Oliver HillOliver Hill, Ph.D., Vice President, Molecular Biology, Apogenix GmbH

Apogenix has developed a fusion protein technology to create hexavalent agonists targeting individual members of the TNFR-superfamily. Compared to conventional approaches using agonistic antibodies, Apogenix compounds mimic the three-dimensional organisation of the natural ligands (the TNFSF proteins). Consequently, their activity does not rely on secondary crosslinking events in vitro nor in vivo. We will present the molecular engineering concept and the current results obtained for the TRAIL-R-, CD40- and CD27-agonists.

12:20 Humanized Mice for Evaluation of
Immuno-Oncology Therapeutics

Brian_SoperBrian Soper, Ph.D., Technical Information Scientist, The Jackson Laboratory

JAX In Vivo Pharmacology Services has combined the human CD34+ hematopoietic stem cell engrafted NSGTM (005557) and NSGTM-SGM3 (013062) mice with human patient derived xenograft (PDX) to create two new platforms for humanized preclinical studies in immuno-oncology. Non-HLA matched PDX tumors grow well, despite concerns over transplant rejection. When treated with Keytruda®(pembrolizumab), an antibody that blocks PD1/PD-L1 binding, tumor growth was significantly diminished. This showed human T cells could be induced to respond to PDX following treatment with a check-point inhibitor. The humanized mouse platform enables further research into both the basic biology and development of therapeutics in human immuno-oncology.

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

13:20 Session Break


IMMUNE CHECKPOINT INHIBITORS

14:15 Chairperson’s Opening Remarks

Björn Frendéus, Ph.D., CSO, BioInvent International AB


KEYNOTE PRESENTATION

14:20 Immune Regulation at the Tumour Site Defining the Interplay between Therapy and the Tumour Microenvironment

Sergio A. QuezadaSergio A. Quezada, Ph.D., Professorial Research Fellow, UCL Cancer Institute

In recent years, a number of publications have demonstrated the essential role that the tumour microenvironment and Fc Receptors play in the in vivo activity of checkpoint targeting antibodies. In this talk we will discuss novel developments in this area relating to the mechanism of action and the development of immune modulatory antibodies, and combinations that promote intra-tumoural Treg with maximal modulatory activity.

14:50 Identification of Checkpoint Inhibitors to Antibody Therapy Regulatory T Cells and Myeloid-Derived Precursors

Björn FrendéusBjörn Frendéus, Ph.D., CSO, BioInvent International AB

A patient-centric phenotypic discovery platform for identification of antibody:target pairs with superior immune cell modulatory activity is described. F.I.R.S.T™ utilizes the high-affinity human antibody library n-CoDeR®, primary cancer-patient’s cells, differential biopanning, and state-of-the-art in vitro and in vivo oncoimmunology models, to identify novel receptors and receptor functions. Preclinical PoC has been obtained through identification of the antibody checkpoint inhibitor (FcγRIIB) as a prime target to overcome antibody drug resistance in lymphoma. Current focus is on identifying targets and mAb capable of specifically deleting cancer Treg cells, or re-educating tumor-associated myeloid cells, to help improve anti-cancer immunity.

15:20 Refreshment Break with Exhibit and Poster Viewing

16:00 Monoclonal Antibodies Targeting Innate Immunity Checkpoint Receptors

Nicolai WagtmannNicolai Wagtmann, Ph.D., CSO, Innate Pharma

NK cells can recognise and kill tumour cells, while sparing healthy tissues. In patients with Acute Myeloid Leukemia, NK cells can prevent tumour relapse and significantly prolong survival, providing a rationale for developing targeted therapeutics that boost NK cell-mediated anti-tumour activity. The talk will describe the rationale and mode-of-action of some of the first-in-class therapeutic antibodies targeting NK cell checkpoint receptors that Innate Pharma is developing for treatment of cancer.

16:30 Anti-Regulatory T Cells: An Alternative Approach to Target Immunosuppressive Mechanisms

Mads Hald AndersenMads Hald Andersen, Ph.D., D.Sc. Tech., Professor, Director, Centre for Cancer Immune Therapy, Copenhagen University Hospital

We have recently described how these naturally-occurring specific T cells recognise both regulatory immune cells as well as malignant cells. The ability of self-reactive T cells to react to and eliminate regulatory immune cells can influence general immune reactions. Thus, utilisation of e.g. IDO- or PD-L1-derived T-cell epitopes may represent an attractive vaccination strategy for targeting cancer cells and for boosting the clinical effects of additional anti-cancer immunotherapy.

17:00 Problem Solving Roundtable Discussions

Table 1: Fcγ Receptors and Therapeutic Antibody Function

Moderator: Ann White, Ph.D., Senior Research Fellow, Faculty of Medicine, Cancer Sciences Unit, University of Southampton

  • Antibody isotype and therapeutic function
  • Activatory versus inhibitory FcγR binding
  • Target deletion, blocking and agonistic receptor engagement
  • Combination therapies: Can multiple mechanisms be exploited?

Table 2: Pros and Cons of Immunocytokine-Based Immunotherapeutics

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

  • Rationale for choice of immunocytokines and how they can act in synergy
  • MOA of the immunocytokines in inducing both local and systemic responses
  • Benefits of using immunocytokines as opposed to ADCs
  • Means of overcoming the challenges of dose limitation and side effects

Table 3: Challenges with Targeting Immune Checkpoint Inhibitors

Moderator: Sergio A. Quezada, Ph.D., Professor and Research Fellow, UCL Cancer Institute

  • Different ways in which the immune response is “checked” in cancer
  • Screening antibodies to the desired target
  • Finding appropriate mouse models for proof-of-concept
  • Finding good antibody-screening assays

Table 4 Challenges of CAR T-Cell Immunotherapies

Moderator: Martin Pule, Ph.D., Senior Lecturer, Haematology, UCL Cancer Institute

  • Different CAR T-cell approaches and their limitations
  • Target selection, screening and validation for targeted delivery
  • Means of overcoming the need for a customized approach
  • Platform development, and product optimization
  • Biomarkers for safety and efficacy
  • Risk of cytokine release syndrome

18:00 Welcome Reception with Exhibit and Poster Viewing

19:00 End of Day One of Immuno-Oncology


Day 1 | Day 2 | Download Brochure | Short Courses | Speaker Biographies

Tuesday, 15 MARCH

08:30 Chairperson’s Remarks

Sergio A. Quezada, Ph.D., Professor and Research Fellow, UCL Cancer Institute


CHIMERIC ANTIGEN RECEPTOR TECHNOLOGY

FEATURED PRESENTATION

08:35 Engineered T Cells Focusing on Advanced CAR Engineering

Martin PuleMartin Pule, Ph.D., Senior Lecturer, Haematology, UCL Cancer Institute





 

09:05 Cutting Off the Supply Lines: Engineering T Cells to Target the Tumour Vasculature

 Steven_LeeSteven P. Lee, Ph.D., Senior Research Fellow, Institute of Immunology and Immunotherapy, University of Birmingham


09:35 Controlling CAR-T Cell Function in vivo Using Molecular Switches

Aaron FosterAaron Foster, Ph.D., Senior Director, Product Discovery, R&D, Bellicum Pharmaceuticals

Regulating CAR-T survival, persistence and expansion in vivo following adoptive transfer is critical for maximising therapeutic efficacy while also managing CAR-T-related toxicity. We present two molecular switches, inducible Caspase-9 (iCasp9) and inducible MyD88/CD40 (iMC), which can be used as “Off” and “On” signals, respectively, to control T-cell behaviour in vivo using systemic administration of the small molecule dimerising ligand, rimiducid.

10:05 The Humoral Immune Response in Cancer and Translational Implications for the Design of Antibody Therapies

Sophia N. Karagiannis, Ph.D., Senior Lecturer, Translational Cancer Immunology, and Head, Cancer Antibody Discovery and Immunotherapy, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London 

10:35 Coffee Break with Exhibit and Poster Viewing


CYTOKINES / ONCOLYTIC IMMUNOTHERAPY

11:10 Advances with IL-2-Based Cancer Immunotherapies

Onur BoymanOnur Boyman, M.D., Professor, Chairman and Director, Immunology University Hospital Zurich

Interleukin-2 (IL-2) immunotherapy has resulted in some remarkable long-term responses with advanced cancer, but at the high doses used for cancer immunotherapy, it can cause adverse effects mediated via its binding to IL-2 receptor α (also termed CD25), leading to endothelial cell damage and expansion of CD4+ regulatory T cells. I will report on studies on avoiding contact of IL-2 with CD25, while preserving IL-2’s immune stimulatory anti-tumour effects. The current state of the art of IL-2-based cancer immunotherapies, implications, and future research directions will be discussed.

11:40 ADAM17: A Gatekeeper in Immuno-Oncology?

Peter Lowe, Ph.D., Project Leader, Molecular and Cellular Biology, Institut de Recherche, Pierre Fabre

ADAM17 a cell surface sheddase, releases a wide range of membrane bound growth factors, receptors, adhesion molecules, cytokines and chemokines. Deregulated ADAM17 shedding of EGFR ligands including amphiregulin, epiregulin, TGFa and HB-EGF has been implicated in a range of cancers. Recent discoveries demonstrate that ADAM17 also sheds at least fifteen immunoregulatory proteins, enhancing immune suppression and permitting tumour escape from immune surveillance. These will be reviewed in this presentation.

12:10 Immune Responses Following Intrapleural Administration of the Oncolytic Immunotherapeutic HSV, Seprehvir, in Patients with Malignant Mesothelioma.

Joe ConnerJoe Conner, Ph.D., CSO, Virttu Biologics Ltd.

Seprehvir is a clinically active oncolytic immunotherapeutic HSV administered to 93 patients via intratumoural, locoregional and intravenous delivery routes. Preclinical data supports Seprehvir’s oncolytic and immunotherapeutic MoA and its potent combinatorial activities with other cancer therapies including Immune Checkpoint Inhibitors and ACT. Our current phase 1/2a trial of Seprehvir given intrapleurally in MPM is providing fascinating insights into patient immune responses to oncolytic immunotherapy with increased Th1 cytokines and localised immune cell recruitment.

12:40 End of Immuno-Oncology


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For more details on the conference, please contact:

Nicole Lyscom, Ph.D.
Senior Conference Director
Cambridge Healthtech Institute
Tel: +44 7791 866489
Email: nlyscom@healthtech.com

For partnering and sponsorship information, please contact:  

Companies A-K
Jason Gerardi
Business Development Manager
781-972-5452 | jgerardi@healthtech.com

Companies L-Z 
Carol Dinerstein
Director, Business Development
781-972-5471 | dinerstein@healthtech.com

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20-24 March 2017


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CONFERENCE PROGRAMS


DINNER COURSES

"Some of the most promising emergent biopharmaceuticals for cancer therapy include agents capable of selective homing to the tumor environment, as well as drugs capable of selective activation of the immune system against malignant cells."

Dario Neri, Ph.D., Swiss Federal Institute of Technology


"You have put together an amazing meeting."

Sergio A. Quezada, Ph.D., UCL Cancer Institute