2017 Archived Content
The Novel Therapies for Cancer and Emerging Targets track at PEGS Europe will highlight the latest discoveries and innovative strategies for the development of novel biotherapeutics against cancer. A review of recent preclinical and clinical results will
reveal insights into why current strategies fail, analyze mechanisms of action, and identify approaches that will lead to better results. Challenges to the field include the need for patient selection methods to identify who will respond to therapy
and combining approaches to address novel targets in new ways to attack cancer successfully. The field has new energy as evidenced by the recent success of novel compounds in the clinic. New plans for engineering therapeutic modalities that can be
used for intracellular and membrane targets will alleviate the discrepancy that currently exists where a wealth of attractive targets are beyond the reach of protein engineers.
Scientific Advisory Board
Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute
Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital,
Harvard Medical School
Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation
Final Agenda
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THURSDAY 16 NOVEMBER
12:30 Registration
13:00 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 Chairperson’s Opening Remarks
Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute,
NIH
13:35 Shared Target Antigens on Cancer Cells and Tissue Stem Cells: Go or No-Go for CAR T Cells?
Hinrich Abken, Ph.D., Professor, Genetics & Immunology, Center for Molecular Medicine Cologne, University
of Cologne
‘On-target off-tumor’ toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. We discuss CAR T cell targeting of activation antigens versus lineage
associated antigens on the basis of recent experimental and animal data, in particular in the context of targeting CD30.
14:05 The UniCAR Platform Technology: Turning CAR T Cells On and Off
Michael P. Bachmann, Ph.D., Director, Institute of Radiopharmaceutical Cancer Research; Head, Radioimmunology,
Helmholtz Zentrum Dresden Rossendorf HZDR
Adoptively transferred conventional CAR T cells remain active in patients and can cause life threatening side effects. In contrast, activity of UniCAR T cells is dependent on the administration of a target module (TM). TMs are bispecific fusion molecules
consisting of an epitope recognized by the UniCAR and a binding domain directed to the respective tumor antigen. After elimination of TMs UniCAR T cells automatically switch off again.
14:35 Can
Severe Adverse Events of CAR-Ts be mitigated through Product Design?
Paula Salmikangas, Director, Biopharmaceuticals and ATMPs, NDA Advisory Board, NDA Group
Clinical development and commercialization of CAR-T products has been hampered by the SAEs caused by high activity of the CART-cells and simultaneous lysis of large tumor loads. This has led to search for technologies to better control the products
but little attention has been given to the product design. Is it time to look into the cell products and discuss whether the most severe AEs could be prevented through proactive product design without compromising efficacy?
15:05 Refreshment Break in the Exhibit Hall with Poster Viewing
15:50 Combination of PD-1/PD-L1 Blockade and Targeting of a Tumor-Specific Carbohydrate Antigen in a Novel Trifunctional Antibody as a Strategy to Improve Anti-PD-L1 Therapy
Johanna Rühmann, Ph.D., Senior Director, Internal project strategy & Cooperations, Glycotope GmbH
We developed a trifunctional antibody which combines targeting of TA-MUC1 and PD-L1 with a functional Fc-part (PM-PDL). By focusing PD-1/PD-L1 blockade to the tumor and multiplying different modes of action, PM-PDL has the potential to increase efficacy
and broaden patient coverage giving additional benefit compared to the respective monospecific antibody. The results further underline the potential of Fc glyco-optimization to enhance not only cytotoxic but also immunomodulatory antibody effector
functions.
16:20 IO Treatments of Renal Cell Carcinoma: The Changing Landscape
Hans Hammers, M.D., Ph.D., Eugene P. Frenkel M.D. Scholar, Clinical Medicine; Associate Professor, Internal
Medicine, Hematology and Oncology, Kidney Cancer Program, University of Texas Southwestern
The presentation will outline key features of the currently approved immunotherapies like nivolumab and IL2 in RCC. Additionally, the emerging treatment landscape with combination immunotherapies such as other immune checkpoints and VEGF pathway inhibitors
will be discussed.
16:50 End of Day
17:00 Dinner Short Course Registration
17:30-20:30 Recommended Dinner Short Course*
SC6: Engineering of Bispecific Antibodies
*Separate registration required
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FRIDAY 17 NOVEMBER
08:00 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital,
Harvard Medical SchoolX
08:35 The Clinical Efficacy of First Generation Carcinoembryonic Antigen (CEACAM5) Specific CAR T Cells is Limited by Poor Persistence and Transient Pre Conditioning Dependent Respiratory Toxicity
Robert Hawkins, Ph.D., FRCP, Professor, Cancer Research, University of Manchester; Honorary Consultant, Medical Oncology
09:05 CAR T Manufacturing Made Simple
Andrew Kaiser, Ph.D., R&D Manager, Cell & Gene Immunotherapy/Clinical Cell Processing, Research & Development, Miltenyi Biotec GmbH
This presentation will focus on advances in the field of automation applied to cellular therapies and describe how T cells can easily be enriched from blood products, activated, gene-modified, expanded and formulated on a single closed platform with
minimal user interactions or liquid handling. Attributes of the produced cells, such as composition, phenotype in vitro and in vivo function will be shown. Recent developments
will demonstrate that such complex procedure can be carried out in serum free conditions and allow for flexible means of gene-modification that can further enable the field.
09:35 The Role of CD28 in the Rescue of CD8 T Cells by PD-1 Targeted Therapies
Rathi Pillai, M.D., Assistant Professor, Department of Hematology and Oncology, Winship Cancer Institute, Emory
University
Programmed cell death-1 (PD-1) directed therapies activate exhausted CD8 T cells and have become effective treatments in cancer. The costimulatory CD28/B7 pathway is essential for the rescue of exhausted T cells in mouse models of chronic viral infection
and cancer. Most proliferating CD8 T cells in the blood of lung cancer patients treated with PD-1 inhibitors express CD28. CD28 costimulation plays an integral role in T cell rescue by PD-1 therapies.
10:05 Coffee Break with Poster Viewing
Chairperson’s Remarks
Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation
10:35 Design and Construction of Antibody Phage Display Libraries for Therapeutic Antibody Discovery
Juan Carlos Almagro, Ph.D., Founder and Director, GlobalBio, Inc.
Display technologies have had a profound impact in engineering antibodies to treat unmet medical needs, in particular, in the oncology field. This talk will discuss the design and implementation of novel phage display libraries with improved functionality
and capabilities for discovery and optimization of therapeutic antibodies.
11:05 Single Domain Antibodies Targeting Glypicans for Cancer Therapy
Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute,
NIH
We develop inhibitory antibodies that target signaling pathways (e.g. Wnt) responsible for the growth of cancer. This can be done by using single domain antibodies that bind cryptic and buried functional regions in receptors or signaling complexes.
We have studied glypicans (e.g. GPC2, GPC3) as a new class of targets in cancer and made immunotoxins and CAR T cells for the treatment of liver cancer and pediatric cancers.
11:35 Strategies to Inhibit the Intracellular Target Ras with Potent Antibody Mimetic Proteins
Ralph Minter, Ph.D., Director, Fellow, Antibody Discovery and Protein Engineering, MedImmune
Ras mutations are strong oncogenic drivers of many cancers but the target Ras is still not addressed by any current therapies. Inhibition of Ras nucleotide exchange is a novel approach to blocking Ras signaling by locking it in an inactive conformation.
We describe an antibody mimetic, DARPin K27, which blocks Ras using such a mechanism and inhibits downstream signaling and tumour cell growth. K27 and other antibody-like molecules enable us to explore novel strategies to (i) deliver functional
macromolecules into cells and (ii) understand the biological implications of Ras inhibition.
12:05 Sponsored Presentation (Opportunity Available)
12:35 Problem-Solving Breakout Discussions with a Light Snack in the Foyer (View All Breakout Discussions)
Advantages and Risks of Current CAR Technologies
Moderator: Michael P. Bachmann, Ph.D., Director, Institute of Radiopharmaceutical Cancer Research; Head, Dep. Radioimmunology, Helmholtz Zentrum Dresden Rossendorf HZDR
- Conventional CARs
- CRISPR/Cas9
- Anti-EGFR
- Modular approaches
HLA Class I Antigen Processing Machinery Defects and Resistance to Immune Checkpoint Inhibitors
Moderator: Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School
13:35 Session Break
14:00 Chairperson’s Remarks
Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute
14:05 Heterocellular Oncogenic Signaling
Christopher J. Tape, Ph.D., CRUK Career Development Fellow, University College London Cancer Institute
Cancer is a heterocellular disease comprised of mutated cancer cells, stromal fibroblasts, and multiple immune cells. Each of these cell types contribute to tumour biology, but the signaling mechanisms underpinning their malignant behaviour are poorly
understood. We have established cell-specific proteomic technologies to measure cell signaling in heterocellular systems. Using these technologies, we demonstrate how oncogenic driver mutations ‘spread’ their signals across multiple
cell types to drive tumours.
14:35 Ultra-Selective T-Cell Engaging Antibody Circuits (TEAC): A New Approach to Cancer Immunotherapy
Mark Cobbold, M.D., Ph.D., Associate Professor, Massachusetts General Hospital, Harvard Medical School
Cytotoxic T-cells are amongst the most potent arms of the immune response and immunotherapies harnessing these exhibit powerful effects against cancer. Separating toxicity from efficacy remains an ongoing challenge for both CAR T and bispecific T-cell
engaging biologics. Here we describe a new antibody-based approach to selectively engage T-cells at tumor sites using Boolean operator logic based upon antigen and protease target site expression. By applying logic gating, we obviate many of the
current challenges with T-cell engaging antibodies.
15:05 Improving CAR T Cell Function by Reversing the Immunosuppressive Tumor Environment of Pancreatic Cancer
Juan Fernando Vera Valdes, M.D., Associate Professor, Medicine, Baylor College of Medicine
To target pancreatic ductal adenocarcinoma (PDAC), we generated a CAR targeting PSCA. However, PDAC tumors produce inhibitory cytokines (e.g. IL4), which limit CAR T cell persistence and effector function. Thus, to protect our CAR T cells we co-expressed
a custom inverted cytokine receptor (ICR) linking the IL4 receptor exodomain with the IL7 receptor endodomain. The current presentation will summarize the in vitro and in vivo results achieved when combining these modifications.
15:35 New Bispecific Antibodies Targeting Members of the EGFR Receptor Family
Roland Kontermann, Ph.D., Professor, Biomedical Engineering, Institute of Cell Biology &
Immunology, University of Stuttgart
Tetravalent, bispecific antibodies, based on a single-diabody Fc format (scDb-Fc), were generated using a novel neutralizing anti-HER3 antibody recognizing a novel epitope formed domain III and IV combined with antibodies against other members
of the EGFR receptor family. A scDb-Fc targeting HER3 and EGFR potently inhibited activation of both receptors and downstream signals, with possible applications to overcome resistance against EGFR monotherapy by compensatory HER3 signaling.
16:05 End of Conference
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