CAR T, TIL and TCR Therapy

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


07:45 Registration (Foyer A) and Morning Coffee (Foyer D)

Auditorium II

08:30 Chairperson’s Opening Remarks

Maher_JohnJohn 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

Epinat_Jean-CharlesJean-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

Adusumilli_PrasadPrasad 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

Qasim_WaseemWaseem 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.

OxfordGenetics 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)

Auditorium II

11:15 Developing Next Generation Autologous and Allogeneic CAR T Cells without Gene Editing

Sotiropoulou_PeggyPeggy 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

Abken_HinrichUniv.-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

Thistlethwaite_FionaFiona 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.

JacksonLab_URL 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

Norell_HaakanHaakan 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)

Auditorium II

16:15 Using Insight into TCR Functioning for an Improvement of CARs

Schamel_WolfgangProf. 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

Hoet_René-001Prof. 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?

Tayton-Martin_HelenHelen 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


08:00 Registration (Foyer A) and Morning Coffee (Foyer D)

Auditorium II

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

Hawkins_RobertRobert 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

Anderson_JohnJohn 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

Doherty_DerekDerek 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

Madakamutil_LouiLoui 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*

17:3020:30 Dinner Short Courses

Recommended Short Course*

SC9: T Cell Therapies: Current Field, Challenges and Future Directions - LEARN MORE

*Separate registration required.