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Immuno Oncology Europe
Immuno Oncology Europe

Novel Approaches for Cancer track header

 

Novel Approaches for Cancer track header

 

本議程將介紹TCR對癌症抗原的無限強化工程、改造T細胞以表現專一癌症標的嵌合性抗原接受器(CAR-T)、以T細胞CD3抗體為標的的雙特異性抗體、腫瘤浸潤淋巴球等領域的最新研究成果。近來多數研究雖著重於B細胞白血病與多發性骨髓瘤,但對於較難治療的實體腫瘤標的化相關研究仍有所進展。

適切標的的辨識與檢驗、交叉反應的克服手段、功效的強化工程、臨床前模型、臨床研究的設計與數據、使用T細胞的產品製造與供給、實體腫瘤標的化等相關個案研究也將在會期中發表。

3月20日

07:30 Conference Registration and Morning Coffee

08:30 Chairperson's Opening Remarks

David Gilham, Ph.D., Vice President, Research and Development, Celyad S.A.

嵌合性抗原接受器技術:以專一性及安全性為中心

KEYNOTE PRESENTATION

08:40 CAR-T Cells: From Basic Research to Cancer Treatment

Zelig_EshharZelig Eshhar, Ph.D., Chair, Cancer Immunotherapy, Research and Development, Sourasky Medical Center, Tel Aviv

Our laboratory pioneered and developed the "T-Body" approach that was later renamed as CAR-T cell and has recently been used in clinical trials to fight cancer. The genetically-engineered T cells have already shown to effectively kill and eliminate patients' lymphomas and leukaemias where about 45% of the treated patients recovered. We applied CAR-T cells to solid tumours constituting a major challenge because of damage to healthy tissues due to cross reactivity of the antibodies used to redirect the CARs. Using human xenografts in immunodeficient mice, we focused on different treatment modes. In these models, we optimised the treatment effects and maximised its safety.

09:10 ErbB-Targeted CAR-T Cell Immunotherapy of Cancer: A Strategy to Maximise the Window of Therapeutic Opportunity

John_MaherJohn Maher, M.D., Ph.D., Consultant and Senior Lecturer, Immunology, Cancer Studies, King's College London

We have developed the T1E28z CAR that targets the extended ErbB network and demonstrates anti-tumour activity in several xenograft tumour models. Although it also engages mouse ErbB receptors, intravenous or intratumoural delivery is non-toxic in SCID Beige mice. By contrast, intraperitoneal administration elicits macrophage-dependent cytokine release syndrome. To de-risk this approach, a Phase I trial employing intra-tumoural delivery has commenced in patients with locally advanced/ recurrent head and neck cancer.

09:40 Increased Specificity Using Boolean Logic Gated CARs for Adoptive T-Cell Therapy

Shaun Cordoba, Ph.D., Research Scientist, Autolus

One large limitation when targeting non-haematological cancers is intolerable "on-target off-tumour" toxicity. With this risk of serious adverse effects, CAR therapy has largely been limited to target antigens exclusively expressed on the cancerous tissue or co-expressed on the cancer and non-essential normal tissues. We will discuss novel approaches used to increase CAR T-cell specificity in the absence of expression restricted antigens. This approach promises to open CAR therapy to numerous cancerous tissues where no appropriate antigen has yet been identified.

MaxCyte no tagline 10:10 Presentation to be Announced

10:40 Coffee Break in the Exhibit Hall with Poster Viewing

CAR-T細胞:效能與多重標的化功能的強化

11:20 B Cell Maturation Antigen (BCMA) CAR-T Cells for Patients with Multiple Myeloma

Katherine_SeidlKatherine J. Seidl, Ph.D., Director, Immunotherapy, bluebird bio

B cell maturation antigen (BCMA) is expressed on most multiple myeloma (MM) cells. We developed lentiviral vectors expressing chimeric antigen receptors (CARs) with anti-BCMA single chain variable fragment (scFv) using 4-1BB and CD3zeta T cell signaling domains. We selected anti-BCMA CAR (bb2121) for clinical development. Ex vivo culture of bb2121 T cells with a PI3K inhibitor leads to enhanced efficacy in vivo and thus represents an attractive option for next-generation CAR-T cell products.

11:50 Exploiting NK Receptors for Adoptive T (CAR T) Cell Therapy

David_GilhamDavid Gilham, Ph.D., Vice President, Research & Development, Celyad S.A.

The early phase clinical success reported with CD19 Chimeric Antigen Receptor (CAR) T cell therapy has driven a surge of interest in the exploitation of CARs for therapy beyond B cell malignancies. CARs typically exploit antibody based targeting technology ensuring a high degree of specificity for a single tumour antigen. This specificity is attractive but also limits the range of tumours that may be targeted by a single receptor. CARs exploiting natural receptors such as the natural killer group 2D (NKG2D) which target 8 different ligands provides an extension of the CAR approach that enables a broader spectrum of tumour targeting by a single receptor. The NKR-2 receptor is a fusion of the NKG2D receptor with CD3z and in pre-clinical models effectively challenges established haematological and solid tumours. These concepts will be discussed along with an outline of the early clinical development of NKR-2 cell therapy.

12:20 Sponsored Presentation (Opportunity Available)

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

13:20 Session Break

次世代CAR-T細胞/生產策略

14:15 Chairperson's Remarks

John Maher, M.D., Ph.D., Consultant and Senior Lecturer, Immunology, Cancer Studies, King's College London

14:20 Of CARs and TRUCKs: The Next Generation of CAR-T Cell Therapy

Hinrich_AbkenHinrich Abken, Ph.D., Professor & Head, Research, Molecular Medicine, University of Cologne

Cancer cells which lack the cognate antigen are invisible to CAR-T cells and thus may contribute to deadly tumour relapses. We discuss the fourth generation of CAR-T cells, so called TRUCKs, which release inducible IL-12 upon CAR engagement in the targeted tumour lesion. Locally accumulating IL-12 in turn attracts an innate immune cell response towards those cancer cells that are invisible to CAR T cells. The strategy combines antigen-redirected immunotherapy with an antigen-independent anti-tumour response.

14:50 Challenges in Moving CAR-T and TCR Therapies from Clinical to Commercial

Bo_KaraBo Kara, Ph.D., Head, Process Development, Cell Gene Therapy CMC, GlaxoSmithKline

Adoptive immunotherapies are demonstrating remarkable 'curative' benefit to patients during clinical development. Although 'fit for purpose' processes and analytics underpin this early phase of development, significant CMC challenges exist in moving these therapies to commercial 'scale'. This presentation will outline strategies and approaches to deliver commercial manufacturing to ensure patient access to these groundbreaking medicines.

15:20 Refreshment Break in the Exhibit Hall with Poster Viewing

T細胞基因工程

16:00 Cancer Therapy with Engineered T Cells

Hans_StaussHans Stauss, M.D., Ph.D., Professor and Director, Immunity & Transplantation, University College London

Immunotherapy has transformed cancer treatment in the past years by achieving clinical responses in patients who have failed all available conventional therapies. T cells can specifically recognise target antigens that are either present on the surface of cancer cells or expressed intracellularly. The purpose of this presentation is to review the genetic engineering technologies that have been developed to produce therapeutic T cells for antigen-specific immunotherapy of cancer.

16:30 Genetically-Engineered T Cells for Cancer Treatment

Chiara_BoniniChiara Bonini, Ph.D., Universita Vita-Salute San Raffaele and Ospedale San Raffaele, Milan

This presentation will outline the unique gene transfer and gene editing technology that we use together with the identification of cell surface and intracellular target antigens. This approach removes the original TCRs from the T cell and thereby enhances efficacy and reduces the risk of toxicity of adoptive cellular immunotherapy. Results and future perspectives will be presented and discussed.

17:00 Problem Solving Roundtable Discussions

Table 1: Immune Cell Engagers: Targeted Treatment in Synergy with Additional Immunotherapies

Moderator: Martin Treder, Ph.D., CSO, Affimed

Table 2: Enhancement of Specificity and Efficacy of CAR-T Cells

Moderator: Zelig Eshhar, Ph.D., Chair, Cancer Immunotherapy, Research and Development, Sourasky Medical Center, Tel Aviv

Table 3: How the Industry Can Benefit from Tumour-Infiltrating Lymphocyte Technology

Moderator: Andrew Sewell, Ph.D., Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine 

Table 4: Preclinical Models for Safety Assessment of Immunotherapies

Moderator: Joseph Dukes, Ph.D., Head, Preclinical Biology, Cell Biology, Immunocore Ltd.

Table 5: T-Cell Product Manufacturing Challenges to Anticipate

Moderator: Bo Kara, Ph.D., Head, Process Development, Cell Gene Therapy CMC, GlaxoSmithKline

18:00 Welcome Reception with Exhibit and Poster Viewing

19:00 End of Day One of Novel Approaches for Cancer

3月21日

08:30 Chairperson's Remarks

Kerry Chester, Ph.D., Professor, UCL Cancer Institute

TCR(T細胞受體), TIL(腫瘤浸潤免疫細胞), 其他 CAR-T

08:35 Utilising in vitro Preclinical Packages for Assessment of TCR-Based Bispecific Biologics: Experience, Application and Predictability

Joseph_DukesJoseph Dukes, Ph.D., Head, Preclinical Biology, Cell Biology, Immunocore Ltd.

TCRs can recognise peptides derived from intracellular proteins, presented by Class I MHC on the surface of target cells, thus offering a unique advantage over current antibody therapies. Such peptides are short, 2D in nature and typically human specific. Therefore traditional in vivo models are unsuitable for safety assessments. Immunocore's in vitro preclinical approach to this challenge will be discussed including the predictability of this method, along with potential challenges.

FEATURED RESENTATION

09:05 Crystal Ball Gazing: What Successful Tumour Infiltrating Lymphocyte Therapy Teaches Us About the Future of T-Cell Therapy? 

Andy_SewellAndrew Sewell, Ph.D., Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection and Immunity, Cardiff University School of Medicine

 Treatment of end stage end-stage metastatic melanoma with tumour infiltrating lymphocyte (TIL) therapy currently results in a complete, lasting remission in >20% of patients with a partial remission and disease steadying in a further third of patients. We have dissected the T-cell responses to tumour from patient cures and made some unexpected findings that might indicate how and why this therapy is sometimes successful.

 

 

09:35 Panel Discussion: Pros and Cons of the Different Approaches: CAR Ts, Modified TCRs and TILs

Panelists:
Kerry_ChesterKerry Chester, Ph.D., Professor, UCL Cancer Institute


Joseph_DukesJoseph Dukes, Ph.D., Head, Preclinical Biology, Cell Biology, Immunocore Ltd.


Bo_KaraBo Kara, Ph.D., Head, Process Development, Cell Gene Therapy CMC, GlaxoSmithKline


John_MaherJohn Maher, M.D., Ph.D., Consultant and Senior Lecturer, Immunology, Cancer Studies, King's College London


Andy_SewellAndrew Sewell, Ph.D., Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection and Immunity, Cardiff University School of Medicine


  • Relative limitations and strengths of these approaches
  • Challenges with specificity and off-site toxicity
  • Potential for attacking solid tumours
  • Can these approaches be automated and simplified
  • Possibilities for non-personalised therapies
  • Preclinical and clinical challenges to anticipate

10:05 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

T細胞的雙特異性抗體

11:10 Engaging Innate and Adaptive Immunity to Fight Cancer

Martin_TrederMartin Treder, Ph.D., CSO, Affimed

Bispecific immune cell engagers developed through Affimed's proprietary antibody platform are well differentiated not only through their bivalent, high avidity binding and specificity, but also due to their lack of competition with circulating IgGs, resulting in significantly stronger activation and modulation of NK or T cells. Preclinical experiments for Affimed's lead candidate, AFM13, a prototypic NK-cell engager currently in Phase II clinical development, have demonstrated synergistic efficacy of AFM13 in combination with checkpoint modulators such as anti-PD-1 antibodies, resulting in activation of both innate and adaptive immunity.

11:40 Next Generation Multi-Specifics

Tariq_GhayurTariq Ghayur, Ph.D., Distinguished Research Fellow, DVD-Ig and Novel Biologics, Global Biologics, AbbVie, Inc.


12:10 Mechanistic Mathematical Model for Bispecific Antibody Interaction with Cellular Targets: The Role and Importance of Lateral Diffusion on the Cell Membrane

Armin_SeppArmin Sepp, Ph.D., Senior Scientific Investigator, Systems Modeling and Translational Biology, GlaxoSmithKline

Bispecific antibodies can specifically bind to the cells expressing two different membrane-bound target antigens even when the average distance between them exceeds the reach of the Fab arms of the mAb. This can be understood from first principles as the cross-linking of targets afforded through their lateral diffusion in cell membrane bilayer. The model can be used to devise the optimal affinities for a bispecific mAb.

12:40 End of Novel Approaches for Cancer

 

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