Winning Strategies for CAR T, TIL and TCR Therapy banner

- CAR-T细胞疗法、TIL疗法、TCR疗法 -

In the past year, the CAR T-cell therapy field has heated up considerably with two recently approved therapies, Kymriah™ and Yescarta™. Efforts to design CAR, TCR and TILs with greater targeting precision, safety profiles and efficacy are leading to a new generation of improved products that will continue to propel the field forward. Come to CHI’s Inaugural Winning Strategies for CAR T, TIL and TCR Therapy track at the PEGS Europe Summit to learn engineering updates, clinical progress and streamlined manufacturing that promise to greatly advance T-cell therapies forward.


Final Agenda

WEDNESDAY 14 NOVEMBER

07:45 Registration and Morning Coffee

ADVANCING T-CELL THERAPIES TO THE CLINIC

08:30 Chairperson’s Remarks

John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London

08:35 T4 Pan-ERB-Targeted CAR T-Cell Immunotherapy of Head and Neck Cancer: Phase I Trial Results

John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London

T4 immunotherapy comprises T-cells that have been engineered to co-express (i) T1E28ζ, a CD28+CD3ζ CAR that engages 8 of 9 ErbB homo- and heterodimers and (ii) 4αβ, a chimeric cytokine receptor consisting of the IL-4Rα ectodomain coupled to the IL-2Rβ endodomain. To de-risk T4 immunotherapy, a dose-escalation intra-tumoral Phase I clinical trial was commenced in SCCHN patients, without lymphodepletion. An update on the trial will be provided.

09:05 The Next Generation of CAR T-Cells

Hinrich Abken, PhD, Professor, Genetics & Immunology, Center for Molecular Medicine Cologne, University of Cologne

Chimeric antigen receptor (CAR) modified T cells substantially reduced the tumor burden in early phase trials and induced spectacular and lasting remissions. We discuss recent developments in the fourth generation of CAR T cells, so called TRUCKs, which release an inducible IL-12 and/or IL-18 upon CAR engagement in the targeted tumor lesion and present a new CAR format to shape the T cell maturation in a specific fashion.

09:35 NKG2D CAR T-Cell Therapy: Developing an Autologous and Allogeneic CAR T Approach Exploiting the Targeting Capacity of the Innate Immune System

David Gilham, PhD, Vice President, R&D, Celyad

The ability of the Natural Killer activatory receptor NKG2D to bind eight different ligands that are frequently over-expressed in tumors makes this receptor an attractive candidate for CAR T cell development. Our initial observations of clinical response in patients with relapsed/refractory Acute Myeloid Leukemia after treatment with CYAD-01, a CAR T cell employing NKG2D for targeting, provides support for the potential for this approach. Our clinical plans to fully explore NKG2D involve autologous approaches and also allogeneic CAR T approaches that do not involve gene editing methodologies and these will be discussed.

10:05 Target Specificity Screening of CAR T-Cells Using Human Cell Microarray Technology

Mark Aspinall-O’Dea, EMEA, Business Development Manager, Retrogenix Limited

Human cell microarray screening enables the discovery of both primary cell surface receptors as well as potential off-targets for a variety of biologics including: peptides, antibodies, proteins, CAR T and other cell therapies. Case studies will demonstrate the utility of the technology in identifying novel, druggable targets as well as in specificity screening for antibodies, scFvs and CAR T cells to aid safety assessment and provide key data to support IND submissions.

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

11:15 Targeting the Tumour Vasculature with CAR T-Cells

Steven P. Lee, PhD, Senior Cancer Research Fellow and Training Lead for the Birmingham CRUK Cancer Centre, Institute of Immunology and Immunotherapy, University of Birmingham

To improve CAR T-cell therapy for solid tumours, rather than targeting malignant cells directly, we are developing CARs to target markers on the tumour vasculature. Having identified the C-type lectin CLEC14A to be selectively overexpressed on tumor vasculature, we have generated CARs targeting this marker that are safe and effective at inhibiting tumour growth in three mouse models of cancer. We are currently developing the approach for a Phase I trial.

11:45 Imaging CAR T-Cells

Sophie Papa, PhD, Senior Lecturer and Honorary Consultant Medical Oncologist, King’s College London

Clinical translation of CAR/TCR T-cell therapy would be enhanced if we could reliably trace the behavior in vivo of the cell product after infusion. Ideally, this non-invasive assessment of T-cell biodistribution would utilise a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer. Here we demonstrate the utility of the human sodium iodide symporter for temporal and spatial monitoring of CAR T-cell behavior.

12:15 Resistance to Chimeric Antigen Receptor T-Cells for Hematological Malignancies

Marco Ruella, MD, Clinical Instructor, Associate Director, Dr. June’s Laboratory, Center for Cellular Immunotherapies (CCI), Perelman School of Medicine, University of Pennsylvania

Anti-CD19 chimeric antigen receptor T cells (CART19) is now an FDA-approved drug for relapsed leukemia and lymphoma. The approval by the FDA of the first adoptive T cell therapy, the UPenn/Novartis CART19 (CTL019), represents a huge achievement for cancer treatment and paves the way to the use of the CART technology in other cancers and in combination with other agents. However, a significant subset of patients treated with CART19 still does not respond or relapses. In his talk Dr. Ruella will present novel findings in the mechanism of CART19 resistance and show recent data on the development of CART combination strategies to overcome resistance.

12:45 Preclinical Selection of Optimal TCR Candidates for Cancer Immonotherapy

Claudia Wagner, PhD, Asscociate Director, Immunology, Immatics Biotechnologies GmbH

TCR-based immunotherapy is emerging as promising alternative to CAR-T approaches, especially for solid cancers. Our proprietary TCR platform generates TCRs highly specific for XPRESIDENT®-validated tumor antigens. We use unique information from the large XPRESIDENT® collection of healthy tissues and tumor biopsies for the selection of efficient and safe TCR candidates.

13:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

14:15 Session Break

UNCONVENTIONAL APPROACHES TO TCR ENGINEERING

14:30 Chairperson’s Remarks

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine


14:35 KEYNOTE PRESENTATION: The ImmTAC Platform: How Far We Have Come and Where We Are Going

Bent K. Jakobsen, PhD, CSO, Immunocore Ltd.

Immune mobilizing monoclonal TCRs against cancer (ImmTAC™) molecules are a novel class of immunotherapy agent comprised of a soluble T cell receptor (TCR) fused to a T-cell redirecting scFv anti-CD3. ImmTAC molecules offer distinct advantages over antibody- and cell-based formats, including access to a much larger pool of antigens in a soluble platform. The lead ImmTAC molecule, IMCgp100, has demonstrated encouraging preliminary anti-tumour activity in patients with metastatic uveal melanoma.

15:05 Genetic Engineering of Therapeutic T-Cells

Hans J. Stauss, MD, PhD, Director & Professor, Tumor Immunology, Infection & Immunity & Transplantation, Royal Free Hampstead NHS Trust

Effective gene transfer platforms can redirect the specificity of patient T-cells using chimeric antigen receptors (CARs) or T-cell receptors (TCRs). In this presentation, we will demonstrate that optimal TCR expression in engineered T-cells is essential for optimal antigen-specific function. We will combine TCR transfer with the engineering of T-cell effector function and show that this combination approach provides best cancer immunity in a murine model.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

OPTIMIZING ADOPTIVE IMMUNOTHERAPY

16:15 Adoptive Cell Therapy-Based on TILs in the Era of Check Point Inhibitors

Inge Marie Svane, MD, Professor, Director, Center for Cancer Immune Therapy – CCIT, Department of Oncology and Haematology, Herlev Hospital, University of Copenhagen

TIL ACT approach can mediate complete and durable responses in 10%-20% of patients with metastatic melanoma, and can also yield clinical responses in other selected types of solid tumors. The presentation will include data on predictive markers for response, the role of neo-epitopes, immune escape mechanisms, as well as data on TIL ACT in anti-PD1 refractory patients and TIL ACT in combination with check point inhibitors.

16:45 New Broadly Expressed Cancer Targets from Successful TIL Therapy

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine

We have developed two new techniques that allow rapid determination of the ligand recognised by any ‘orphan’ T-cell clone. These techniques have enabled discovery of novel cancer-associated epitopes that are present on the surface of most cancers.

PANEL DISCUSSION: Cellular Therapy vs. Soluble (Antibody and TCR)

17:15 Moderator

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

17:45 Networking Reception in the Exhibit Hall with Poster Viewing

18:45 Problem-Solving Breakout Discussions

19:45 End of Day

THURSDAY 15 NOVEMBER

08:00 Registration and Morning Coffee

IMPROVING SAFETY AND EFFICACY OF CAR T THERAPY

08:30 Chairperson’s Remarks

08:35 Safety Challenges of T-Cell Therapies: The Balance between Efficacy and Safety

Michaela Sharpe, PhD, Head of Nonclinical Safety and Immunotherapy Strategy, Cell and Gene Therapy Catapult

Gene engineered T-cell therapies have the potential to revolutionize the treatment of cancer. The power of these treatments is linked with a distinct set of toxicities both predicted and unpredicted. As these therapies begin to reach more patients, it is critical to develop the nonclinical tools to adequately determine the mechanisms driving these toxicities, to assess the safety risks of candidate products, and to develop strategies for safety management.

09:05 Targeting the T-Cell Receptor β-Chain Constant Region for Immunotherapy of T-Cell Malignancies

Paul Maciocia, PhD, Clinical Training Fellow/BRC Clinical Lecturer in Haematology, Research Department of Haematology, Faculty of Medical Sciences, University College London

T-cell cancers have a poor prognosis with few effective treatments available. We developed a novel immunotherapy based on targeting T-cell receptor β-chain constant domain 1 (TRBC1) or 2 (TRBC2). While normal T-cells contain both TRBC1+ and TRBC2+ compartments, malignancies are restricted to only one. We engineered anti-TRBC1 CAR T-cells, which killed normal and malignant TRBC1+, but not TRBC2+, T-cells in vitro and in vivo. Thus, anti-TRBC immunotherapy could eradicate a T-cell cancer while preserving T-cell immunity.

09:35 CAR T-Cells –What’s Next? From Personalized to “Off the Shelf” CARs

Anat Globerson Levin, PhD, Senior Researcher & Immunology Lab Manager, Immunology Research Lab, Tel-Aviv Sourasky Medical Center

CAR (chimeric antibody receptors) T-cell therapy, pioneered in our lab, is a powerful tool for cancer treatment. This approach has proven very effective in clinical trials in leukemia and lymphoma patients and has recently gained FDA approval to treat certain types of large B-cell lymphoma. Today, the major challenge in the CAR T-cell field is to prevent ‘off-tumor on-target’ toxicity, namely, the risk of damage to the patient’s healthy tissue which expresses the target antigen of the selected CAR. Furthermore, the manufacturing of CAR T-cells under GMP is a focal point for this promising therapeutic modality. As personalized therapies, autologous cell-based therapies pose a distinct set of manufacturing challenges. Protocols must be developed to reduce the number of CAR T-cells needed for a therapeutic effect and treating patients with allogeneic CAR T-cells can facilitate the procedures needed for manufacturing and make CAR T-cell therapy more available for patients. Here, we will present our solution for these three obstacles. We took advantage of the surface expression of several antigens that are widely expressed on multiple myeloma cells and are poorly expressed by hematopoietic stem cells, and generated CAR T-cells with dual specificity, expressing two complementary CARs (double CARs) for the specific and effective treatment of MM and to overcome the ‘off-tumor on-target’ toxicity. We will also present the optimization of CAR T-cell treatments in order to minimize the number of cells administered. Finally, we will present our solution for “Off the Shelf” CARs.

10:05 Sponsored Presentation (Opportunity Available)

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

PANEL DISCUSSION: Cell Therapy, Making It an “Off the Shelf” Therapy

11:15 Moderator

Moderator to be Announced

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Dessert Break in the Exhibit Hall with Poster Viewing

14:00 End of Winning Strategies for CAR T, TIL and TCR Therapy

17:00 Dinner Short Course Registration*

17:3020:30 Dinner Short Courses


Recommended Short Course*

SC10: Engineering of Bispecific Antibodies

Nicolas Fischer, PhD, Head, Research, Novimmune SA

Michela Silacci, PhD, Director, Discovery Research, Covagen AG, part of J&J

By attending this interactive workshop, you will learn about the various approaches used for the engineering of bispecific antibodies and bispecific scaffold-based binding proteins. Different technologies will be compared, and examples for applications of bispecific antibodies in drug development will be presented with a focus on candidates that are currently being evaluated in clinical trials. Opportunities and challenges as well as current trends in the field of bispecific antibodies will be discussed.

*Separate registration required.

* 活动内容有可能不事先告知作更动及调整。

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