Novel Therapies for Cancer and Emerging Targets Track Banner


がんの新たな治療法と標的
臨床研究の成功に向けた効能の改善

このカンファレンスプログラムでは、がんに対応する新たな生物学的治療薬の開発に向けた創薬と技術革新の先進的な戦略が焦点となります。会期中は、前臨床研究と臨床研究の最新の成果を検討し、これまでの戦略が失敗する原因を解明するセッション、作用機序を分析するセッション、より良い転帰へとつながるアプローチを探るセッションなどが予定されています。この分野の課題としては、治療に反応する可能性の高い患者を選ぶ方法の必要性、がんを効果的に治療する新たな手法を用いて新規の標的に対応するための併用法などが挙げられます。この分野では、新たな化合物の臨床試験が成功し、有効性が裏付けられたことで、エネルギーが高まっています。また、細胞内標的と膜標的に対して利用可能な治療法を開発するための新たな計画も生まれており、多くの魅力的な標的がタンパク質工学の埒外にあるという問題に対する現在の見解の相違が緩和される可能性もあります。

Scientific Advisory Board
Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute
David Lowe, Ph.D., Senior Director, R&D, Antibody Discovery and Protein Engineering, MedImmune Ltd
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

11月16日 (木)

12:30 Registration

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

新たなT細胞療法:従来の枠にとらわれない思考

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_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.

14:35 Sponsored Presentation (Opportunity Available)

15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

チェックポイント阻害の新たな考え方

15:50 Using Oncolytic Viruses to Prime Tumours for Sequential Checkpoint Blockade

Adel Samson, MBChB, Ph.D., NIHR Academic Clinical Lecturer (Medical Oncology), Leeds Institute of Cancer & Pathology, University of Leeds

Cancer therapy aimed at immune checkpoint blockade is rapidly changing clinical practice. For drugs targeting the PD-1/PD-L1 axis, key biomarkers of efficacy include tumour PD-L1 expression and lymphocyte infiltration. Here, we describe a novel systemic treatment strategy to enhance the efficacy of checkpoint blockade, by pre-treating patients using oncolytic viruses.

16:20 IO Treatments of Renal Cell Carcinoma: The Changing Landscape

Hans_HammersHans Hammers, M.D., Ph.D., Associate Professor, Internal Medicine, UT Southwestern Medical Center

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

11月17日 (金)

08:00 Registration and Morning Coffee

CAR-T療法が固形腫瘍に効かない理由

08:30 Chairperson's Remarks

Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School

08:35 CAR T Cells and Non-Hodgkin Lymphoma: Novel Clues for Better Treatment Strategies

Ettore_BiagiEttore Biagi, M.D., Ph.D., Associate Professor, Pediatrics, Universita Milano Bicocca San Gerardo Hospital

CAR T cells have gained in the past decade impressive results in terms of disease control in acute lymphoblastic leukemia, both in kids and adults, offering a valid therapeutic strategy for relapsed patients. CD19 looks to be a promising target also for NHL and preliminary clinical data have shown some complete and partial remissions. Nevertheless, the hostile immune-suppressive microenvironment and obstacles in T cell infiltration pose new relevant clinical questions. Combinatorial therapies by using CAR T cells and other immunotherapeutic agents will give novel clues on better refractory NHL treatment strategies in the near future.

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

困難だが成果が見込める新たな標的:腫瘍標的化のための適切な戦略の採用

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

13:35 Session Break

がん標的化分野での進歩

14:00 Chairperson's Remarks

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

14:05 Heterocellular Oncogenic Signaling

Chris_TapeChristopher J. Tape, Ph.D., Junior Group Leader, Cell Communication Team, The Institute of Cancer Research

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 Cancer Immunotherapy in Children and Nonclinical Juvenile Animal Toxicity Studies

Dinah_DuarteDinah Duarte, Pharm.D., Head, Scientific Evaluation Unit, INFARMED, I.P. Portuguese Regulatory Authority for Medicines

Discuss the importance and value of nonclinical juvenile animal studies for therapeutic monoclonal antibodies mainly for oncology products. Share real world experience from available historical data on juvenile animal studies towards paediatric use and build up the experience on utility of juvenile studies in therapeutic area of therapeutic monoclonal antibodies, especially in oncology.

16:05 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.

16:35 End of Conference

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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