The stunning success of CAR T therapy over the past couple of years has spawned a new industry and a proliferation of CAR, TCR and TIL constructs. Engineering efforts are aimed at improving the design, targeting, developability, manufacturing, and scalability
of new formats to solve issues that remain, including improving the safety of immunotherapy, affordability and targeting of solid tumors. The tumor microenvironment and the microbiome are being tapped to predict the efficacy of immunotherapy and optimize
results.
Final Agenda
Scientific Advisory Board
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London
WEDNESDAY 20 NOVEMBER
07:45 Registration (Foyer A) and Morning Coffee (Foyer D)
08:30 Chairperson’s Opening Remarks
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London
08:35 KEYNOTE PRESENTATION: Evolving Manufacturing Concepts and Approaches for Gene-Edited Off-the-Shelf Cell Therapy Product Candidates
Jean-Charles Epinat, PhD, Head, Process Development, Cellectis
This talk will discuss how gene editing is instrumental in moving cell therapies from grafts to off-the-shelf pharmaceuticals, evolving production and control concepts for gene-edited allogeneic cell product candidates, and how to approach manufacturing
of genomically engineered designer cells.
09:05 Quest for Allogeneic CAR T Cells
Prasad
S. Adusumilli, MD, FACS FCCP, Deputy Chief and Associate Attending, Thoracic Surgery; Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center; Associate Professor,
Cardiothoracic Surgery, Weill Cornell Medical Center
The presentation will focus on advances in CAR T-cell therapy and the next steps in translation to clinic with specific focus on the quest for allogeneic CAR T cells. The methods will be discussed. The update on currently available modalities will be
highlighted.
09:35 CRISPR-Edited Allogeneic T Cell Therapy
Waseem Qasim, PhD, NIHR
Professor in Cell & Gene Therapy, Consultant in Paediatric Immunology/BMT, Institute of Child Health & Great Ormond Street Hospital
The wider application of engineered T cells may be advanced by incorporating genome editing steps to overcome HLA barriers to allow the generation of ‘universal’ CAR T cell banks. Transcription activator-like effector nucleases (TALEN) modified
CAR19 T cells are already in clinical testing and further iterations using CRISPR/Cas9 editing are planned. Furthermore, precise chemical deamination effects can be delivered using RNA-guided deactivated Cas, offering the possibility of multiplexed
editing with low risk of translocations.
10:05 Novel Mammalian Display Strategies for the Discovery of Antibody Therapeutics Targeting Integral Membrane Proteins
Nathan Robertson, PhD, Antibody Discovery, OXGENE
We present a novel method of mammalian display involving expression of an antibody library in a population of mammalian cells, wherein each cell displays the target polypeptide on the outer surface. This technology enables screening of large naive libraries
against more intractable membrane proteins while displaying only physiologically relevant epitopes.
10:20 Discovery and Development of Therapeutic Antibodies Against Potassium Channels
Paul Colussi, Vice President, Research, TetraGenetics Inc.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
11:15 Developing Next Generation Autologous and Allogeneic CAR T Cells without Gene Editing
Peggy Sotiropoulou, PhD, Director Research & Development, Celyad
Celyad uses an optimized shRNA technology to generate next-generation autologous and allogeneic CAR T cell therapies. The first autologous product developed is CYAD-02, our next-generation NKG2D-based CAR, showing increased in vivo persistence and anti-tumor activity in animal models. In the allogeneic CAR T cell field, Celyad leverages the shRNA platform to target CD3ζ and effectively knock down TCR expression. This protected animals against GvHD, while enhancing persistence
of allogeneic CAR T cells compared to gene-editing approaches.
11:45 CARs, TRUCKs and Beyond: Novel Strategies to Target Solid Cancer
Univ.-Prof. Dr. Hinrich
Abken, MD, PhD, RCI, Regensburger Centrum für Interventionelle Immunologie, Lehrstuhl für Gen-Immuntherapie, Universitätsklinikum Regensburg
Adoptive therapy with chimeric antigen receptor (CAR)-modified T cells achieved remissions of so far refractory leukemia/lymphoma, however treatment of solid cancer remains challenging. We engineered CAR T cells with an inducible expression cassette to
release a heterologous protein upon CAR signaling. Such TRUCKs or “fourth generation” CAR T cells are going to change our concepts of treating solid tumors and delivering drugs to predefined lesions in the near future.
12:15 Clinical Strategies for Overcoming Challenges of Engineered T Cells in Solid Tumours
Fiona Thistlethwaite, MB, BChir, PhD, MRCP, Medical Oncology Consultant, Experimental Cancer Medicine Team (ECMT); Honorary Senior Lecturer, Division of Cancer Sciences, Faculty of Biology Medicine & Health, The University of Manchester; iMATCH
Director, The Christie NHS Foundation Trust
The remarkable responses seen with CAR T therapy in haemato-oncology malignancies have yet to be replicated in the solid tumour setting. This talk will focus on approaches being taken to overcome the multiple challenges in solid tumours, including lack
of truly tumour-specific surface antigens required for CAR T therapy. TCR T cell therapy is one approach where clinical responses have been demonstrated, indicating the potential for this approach in solid tumours.
12:45 Selected Poster Presentation: CARDIS: Next Generation CAR Discovery
Eleni Chantzoura, PhD, Senior Scientist, Immune Receptor Discovery, AgenTus Therapeutics, Inc.
13:00 Selected Poster Presentation: Half-Life Extended Soluble Adapters for Efficient Re-Targeting of Universal Switch On/Off CAR-T Cells (UniCAR) Against Leukemia and Solid Tumors
Jan Erik Meyer, PhD Student / Doktorand, GEMoaB Monoclonals GmbH
13:15 Luncheon Presentation I: Specificity Screening of Cell Therapies Against Extensive Libraries of Plasma Membrane and Secreted Protein Targets
Diogo Rodrigues Ferreirinha, MSc, European Business Development Manager, Retrogenix Limited
Cell microarray screening of plasma membrane and tethered secreted proteins that are expressed in human cells enables rapid discovery of primary 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 to aid safety assessment and provide key data to support IND submissions.
13:45 Luncheon Presentation II: Utilization of an In Vivo PBMC Humanized Mouse Model for Determining Checkpoint and Bispecific Antibody Related
Cytokine Release Syndrome
James Keck, Senior Director, Innovation & Product Development, The Jackson Laboratory
Although antibodies and CAR-T cell therapies have been successfully used for cancer treatment, they can have adverse effects such as cytokine release syndrome (CRS). Animal models and in vitro assays presently in use do not reliably predict CRS in
patients. We have developed a rapid, sensitive and reproducible novel in vivo humanized mouse model that differentiates human PBMC donors based on CRS response to single agent and combination therapeutics of checkpoint inhibitors and bispecific
antibodies.
14:15 Session Break
14:35 TEGs: A New Avenue in Cellular Immunotherapy
Haakan Norell,
PhD, Director, Discovery, Gadeta B.V.
Identification of generally applicable receptors that specifically target various malignancies remains challenging. Gadeta employs γδTCRs, which are not restricted to a single class of antigen-presenting proteins or dependent on mutation-induced
neoantigens, to resolve this key bottleneck for broader application of engineered T cell therapies. Our product platform, TEG (αβT cells engineered to express a defined Gamma-delta receptor), achieves potent, yet highly specific reactivity
across many different tumor types.
15:05 Non-Viral Genetic Engineering of Cytokine-Induced Killer (CIK) Cells with Chimeric Antigen Receptors (CARs) for the Targeting of Acute Myeloid Leukemia
Sarah Tettamanti, PhD, Centro Ricerca M.Tettamanti, Clinica Pediatrica Ospedale S.Gerardo, Università Milano-Bicocca
In AML, the CAR strategy is still in a challenging phase of clinical development. In this study, we aimed at arming, by the use of a cost-effective and safe non-viral approach, the effector population of Cytokine-Induced Killer (CIK) cells with CAR
molecules targeting CD33 and CD123 AML overexpressed antigens. In vitro and in vivo characterizations have been performed to pre-clinically test this new platform on non-viral
anti-AML CAR-CIK cells.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
16:15 Using Insight into TCR Functioning for an Improvement of CARs
Prof.
Dr. Wolfgang Schamel, Institute of Biology III (Molecular Immunology) and BIOSS Centre for Biological Signaling Studies, University of Freiburg; Centre of Chronic Immunodeficiency, University Medical Centre Freiburg
We (Schamel group) study the mechanisms with which the TCR is activated by ligand binding for many years. Our main finding is that the TCR-CD3 complex exists in two different conformations: the resting inactive conformation and the active conformation.
In fact, basal signaling by the TCR is suppressed by its quaternary structure. This is missing in chimeric antigen receptors (CARs). Furthermore, the different CD3 subunits contain different signaling domains. Again, in the CD3ζ-based CARs,
most of them are missing. Having this in mind, we (TCR2 Therapeutics and Schamel group) have engineered and studied a new format of CARs called TCR fusion constructs (TRuCs). We show that an intact TCR complex can be effectively reprogrammed for
cancer therapy by recombinantly fusing an anti-CD19 scFv to its TCRα, TCRβ, CD3ε, CD3γ, or CD3δ subunit. Respective scFv-TCR fusion constructs (termed TRuCs) were integrated into the TCR complex and expressed on
the surface of T cells. In the presence of CD19-positive tumor cells, fusion constructs based on CD3ε and CD3γ could specifically and potently activate T cells. Despite the absence of extra signaling domains, TRuC-T cells showed
similar in vitro cytotoxicity as CD28- and 4-1BB-based anti-CD19 CAR T cells. A single CD3ε-TRuC-T cell dose greatly extended the survival of mice with Nalm-6 leukemia. In a subcutaneous Raji tumor model,
CD3ε-TRuC-T cells outperformed CAR T cells in terms of anti-tumor activity. Our novel technology for genetically engineering T cells provides an alternative to CARs that can engage the physiological and broad signaling capacity of the
entire TCR complex.
16:45 Development of a Next Generation Immune Checkpoint Modulator towards the Clinic: A Humanized BTN3A Antibody (ICT01) Activating gamma9delta2 T Cells
Prof. Dr. René
Hoet, PhD, CSO, ImCheck Therapeutics
ImCheck Therapeutics is advancing the first activating butyrophilin BTN3A (CD277) antibody towards the clinic. The humanized antibody to BTN3A, ICT01, specifically activates human gamma9delta2 T cells in vitro and
in vivo and is planned to enter Phase I studies in early 2020. Additionally, therapeutic antibodies against 5 novel butyrophilins are currently validated. This opens a completely new space that is clearly different
from the current B7/CD28 superfamily targets and has the potential to become the next generation immune checkpoint modulators.
17:15 TCR T Cell Therapies – What Have We Learned So Far and Where Next?
Helen Tayton-Martin, PhD, MBA, CBO, Adaptimmune
T cell therapy represents a new modality in the battle to treat cancer with immunotherapy as recent approvals have shown. However, the natural method by which T cells activate and kill infected or tumour cells involves engagement between the TCR and
its cognate peptide-HLA complex on the surface of the cell. Starting from this fundamental principle, seeking to understand why it fails in cancer then moving to enhance the fundamental biology of the TCR to enable recognition and killing of cancer
cells (and not normal cells) to produce a T cell product capable of benefiting patients in the real world, has been the focus of Adaptimmune for over 11 years. Today, the company has demonstrated the efficacy of this platform, termed SPEAR T cells
(Specific Peptide Enhanced Affinity Receptor T cells) against solid tumours in synovial sarcoma with more than one product and has shown signs of activity with tumour shrinkage across multiple tumours with all of its three proprietary clinical
programs. It has built a fully integrated capability to identify and validate TCR targets, produce and safely test engineer TCRs, optimise the viral vector to transfer them to patients’ T cells, and the capability to manufacture and release
those T cells products from its own facilities to patients across the US, Canada, the UK, and Europe. It has a Phase II (SPEARHEAD-1) study launching with its MAGE A4-targeted T cells (ADP-A2M4) in 2019 in synovial sarcoma and myxoid round cell
liposarcoma (MRCLS) and has built a bank of translational and correlative immunology expertise informing optimisation of the T cell product for durable efficacy and efficient delivery across multiple tumours with its first second-generation SPEAR
T cell product (ADP-A2M4CD8 – the SURPASS Trial) also launching this year. Every step is an evolution in understanding on the path to produce accessible and safe products capable of benefitting patients and this learning will be the focus
of the presentation.
17:45 Networking Reception in the Exhibit Hall with Poster Viewing (Rio Pavilion)
18:45 Problem-Solving Breakout Discussions*
TABLE 19: Challenge of Combination Drugs with Check Point Inhibitors
Moderator: Prof. Dr. René Hoet, CSO, Imcheck Therapeutics
- Currently there are over 1700 clinical trials with combination therapies with approved check point inhibitors (anti-PD-1, anti-PDL1, anti-CTLA4) with far with limited success
- What can we learn from this?
- How can we improve?
TABLE 20: Cellular vs. Non-Cellular Antibody Therapies
Moderator: John Anderson, PhD, GOSHCC Professor of Experimental Paediatric Oncology, Honorary Consultant Oncologist, UCL Great Ormond Street Institute of Child Health
- Cell therapies versus antibodies
- Towards universal cell therapies
NEW: TABLE 21: Moving T-Cell Therapies
Moderator: Prasad S. Adusumilli, MD, FACS FCCP, Deputy Chief and Associate Attending, Thoracic Surgery; Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center;
Associate Professor, Cardiothoracic Surgery, Weill Cornell Medical Center
- How gene editing is transformative in CAR T-cell therapies?
- What are the main challenges to broaden the scope of T-cell therapies?
- Industrializing cell therapy: Are T-cells a case that can be expanded to other cell therapies?
19:45 End of Day
THURSDAY 21 NOVEMBER
08:00 Registration (Foyer A) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London
08:35 Developing TIL-Based Treatment for Solid Tumours
Robert Hawkins,
MB BS, MRCP, PhD, FRCP, Cancer Research UK Professor, Medical Oncology, University of Manchester; Honorary Consultant, Medical Oncology, Christie Hospital; Chief Executive Officer and Director, Immetacyte Ltd.
This talk will address the background to TIL therapy and potential benefits in solid tumours, clinical results in melanoma, pre-clinical data in other tumours, and engineering TIL to produce second-generation products.
09:05 Gamma Delta CAR T Cells Engineered for Avoidance of Toxicity and Dysfunction
John Anderson,
PhD, GOSHCC Professor of Experimental Paediatric Oncology, Honorary Consultant Oncologist, UCL Great Ormond Street Institute of Child Health
Gamma delta T lymphocytes combine properties of innate and adaptive immunity. Through exploiting the natural ability of gamma delta T cell receptors to distinguish normal from diseased cells in a MHC unrestricted manner, engineering approaches can
provide additional stimulatory signals in a tumour antigen-dependent manner that fine-tune tumour reactivity. Unlike conventional T cells, gamma delta T do not provoke graft versus host disease, so gamma delta CAR T are a promising approach for
development of allogeneic universal cell products.
09:35 Innate T Cells for the Treatment of Disease
Derek G. Doherty,
PhD, Associate Professor, Trinity College Dublin; Head, Discipline of Immunology, Trinity Translational Medicine Institute, St. James’s Hospital
Innate T cells are unconventional T cells that recognise non-peptide antigens using semi-invariant T cell receptors. Some innate T cells have powerful antitumor activities and are being targeted in clinical trials in humans. They have advantages over
conventional T cells in that they can be activated using conserved antigens; they rapidly, powerfully, and selectively activate adaptive immune responses; and they are unlikely to mediate allogeneic tissue rejection.
10:05 Selected Poster Presentation: ImmTAC™: Engineering Bispecific TCR-Based Fusion Proteins, with High Specificity and Affinity, to Treat Cancer
Elin Sivertsson, PhD, Senior Scientist, Protein Engineering, Immunocore Ltd.
10:20 Selected Poster Presentation: Gamma Delta TCR Anti-CD3 Bispecific Molecules (GABs) as Novel Immunotherapeutic Compounds
Eline van Diest, Translational Immunology, University Medical Center Utrecht
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
11:15 NKTR-255: A Polymer-Conjugated IL-15 that Enhances CAR T Efficacy in Murine Models
Loui
Madakamutil, PhD, Senior Vice President, Head of Biology and Preclinical Development, Nektar Therapeutics
CAR T cells have transformed the treatment paradigm in hematological malignancies, especially in the relapse refractory disease setting. Increasing evidence suggests that CD19 CAR T agents have issues with durability when infused in patients and better
outcome is correlated with durable and enhanced uptake of CAR T cells after their infusion. Several studies indicate that T cell homeostatic cytokines, like IL-15 and IL-7, have correlation to CAR T cell survival and engraftment in patients by
providing stemness and long-term survival for the CAR T cells. NKTR-255 is a polymer-conjugated IL-15 that retains binding affinity to IL15Rα and exhibits reduced clearance to thereby provide a sustained pharmacodynamic response to CD8 memory
T cells and NK cells. This presentation will cover our investigation of NKTR-255 to synergize and provide long term benefit for CAR T products in preclinical model systems.
NEW 11:45 CAR T-Cell Immunotherapy of Solid Tumours: Lessons from the Clinic and Lab in Parallel
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
14:00 End of Winning Strategies for CAR T, TIL and TCR Therapy
17:00 Dinner Short Course Registration*
17:30 – 20:30 Dinner Short Courses
Recommended Short Course*
SC9: T Cell Therapies: Current Field, Challenges and Future Directions - LEARN MORE
*Separate registration required.