2017 Archived Content

Novel Therapies for Cancer and Emerging Targets Track Banner


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

THURSDAY 16 NOVEMBER

12:30 Registration

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

NEW T CELL THERAPIES: OUT OF THE BOX THINKING

13:30 Chairperson’s Opening Remarks

Mitchell HoMitchell 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_AbkenHinrich 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_BachmannMichael 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.

NDA 14:35 Can Severe Adverse Events of CAR-Ts be mitigated through Product Design?

Paula_SalmikangasPaula 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

NEW THINKING FOR CHECKPOINT BLOCKADE

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_HammersHans 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

FRIDAY 17 NOVEMBER

08:00 Registration and Morning Coffee

WHY DOESN’T CAR T THERAPY WORK IN SOLID TUMOURS YET?

08:30 Chairperson’s Remarks

Soldano FerroneSoldano 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_PillaiRathi 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

DIFFICULT AND NEXT GOOD TARGETS: ARE WE USING THE RIGHT STRATEGIES TO TARGET TUMOURS?

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 HoMitchell 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 MinterRalph 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

IMPROVEMENTS IN TARGETING CANCER

14:00 Chairperson’s Remarks

Kerry ChesterKerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute


14:05 Heterocellular Oncogenic Signaling

Chris_TapeChristopher 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_CobboldMark 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_VeraJuan 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 KontermannRoland 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