Cambridge Healthtech Institute’s 4^th Annual

Adoptive T-Cell Therapy

Effective and Unconventional Strategies

21-22 March 2019

The therapeutic potential of adoptive T-cell therapy was first acknowledged a couple decades ago, but it was only last year that we transformed adoptive T-cell therapy into a viable therapeutic option for patients by the two CAR T-cell therapies approved by the FDA. Although this is a very exciting time for adoptive T-cell therapy, there is still much to be done to reach its full potential. Cambridge Healthtech Institute’s 4th Annual Adoptive T-Cell Therapy will gather experts in the field to address clinical progress, discuss strategies to reduce toxicity, increase efficacy, production and cost-effectiveness, along with showcasing emerging unconventional T-cell therapies.

Final Agenda

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THURSDAY 21 MARCH

12:15 Registration

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

TILS, TCRS AND GAMMA DELTA

14:00 Chairperson’s Opening Remarks

Reno Debets, PhD, Associate Professor, Laboratory of Tumor Immunology, PI, Medical Oncology, Erasmus MC-Cancer Institute

14:05 Preclinical Data and Clinical Plan for Developing Tumour Infiltrating Lymphocytes (TIL) for Solid Tumor Indication

Robert Hawkins, MB BS, MRCP, PhD, FRCP, Cancer Research UK Professor, Medical Oncology, University of Manchester; Honorary Consultant, Medical Oncology, Christie Hospital

14:35 TCR-Engineered T Cells Combined with T Cell Co-Stimulation to Treat Solid Tumors

Reno Debets, PhD, Associate Professor, Laboratory of Tumor Immunology, PI, Medical Oncology, Erasmus MC-Cancer Institute

To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs and, at the same time, include strategies that restore or enhance accumulation and activation of T cells in tumor tissues. Here, we present our recent preclinical and translational studies to enhance TCR-engineered T cell therapy, its combination with T cell co-stimulation, and, when available, first data of a clinical T cell therapy trial to treat patients with melanoma and head-and-neck cancer (starts in 2018 Q4).

15:05 Introduction to Gamma Delta T Cells and Their Potential for Cancer Immuno-Therapy

Oliver Nussbaumer, PhD, Head of Cell Research, Cell Research, GammaDelta Therapeutics Ltd.

Human tissues contain large numbers of immune cells that play a key role in maintaining tissue integrity, protecting against transformation and infection. Lately, it has been shown that γδ T cells recognize and respond to tissue stress such as cancer, a process called lymphoid stress surveillance. We have developed methods to investigate the properties of tissue resident γδ T cells making them available for the first time for clinical development.

15:35 Presentation to be Announced

16:05 Networking Refreshment Break

NOVEL TARGET AND TECHNOLOGIES FOR T CELL THERAPIES

16:30 Novel Targets, Receptors & Cellular Platforms for Cancer Immuno-Therapy

Mark A. Exley, PhD, Vice President, Cellular Immunology, AgenTus Therapeutics, Inc.

Adoptive cell therapy is making inroads into previously untreatable cancers. However, toxicities along with emerging relapses, high cost of goods and logistical issues with autologous ACT suggest there is much to do. AgenTus is developing novel tumor target identification, T cell receptor and CAR platforms, and allogeneic cellular delivery systems. A new class of phospho-tumor targets, TCRs recognizing PTTs, and our cell platform will be described. Clinical trials are planned.

17:00 Novel Methods of Transgene Delivery, CAR Design, Optimization and Target Validation

Thomas Nerreter, PhD, Senior Research Fellow, Internal Medicine II, University Hospital Wuerzburg

While CD19, approved for the therapy of several hematologic malignancies, is still by far the best-studied target for CAR T therapy, other candidates are just around the corner, addressing hematologic and solid tumors that are not susceptible to CD19 CAR T treatment. We will hear on these candidates and novel methods of transgene delivery, CAR design and optimization as well as target validation.

17:30 CRISPR/Cas9 Enables the Efficient Production of Allogeneic CAR-T Cells Engineered to Contain Multiple Genome Edits to Enhance Therapeutic T-Cell Function

Jonathan Terrett, PhD, Head of Immuno-Oncology, Crispr Therapeutics Inc

The CRISPR/cas9 system allows for rapid assessment of the consequences of perturbing genes while at the same time deriving potentially lead guide RNAs for cell and gene therapies. This has enabled the efficient development of allogeneic CAR T therapeutics containing genome edits designed to overcome potential immunological and tumor micro-environment issues. Data for allogeneic CAR Ts targeting leukemias/lymphomas and solid tumors will be discussed.

18:00 Close of Day

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Recommended Dinner Short Course*

18:30 - 21:30

SC3: Managing the Challenges of Bioassays for Immuno-Oncology - Detailed Agenda

SC4: T Cell Therapies: Current Field, Challenges and Future Directions - Detailed Agenda

*Separate registration required

FRIDAY 22 MARCH

NEXT-GENERATION T CELL THERAPY

8:00 Morning Coffee

8:30 Chairperson’s Remarks

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

8:35 KEYNOTE PRESENTATION: Cars, Trucks and Beyond: The Next Generation of Adoptive T-Cell Therapy

Hinrich Abken, PhD, Professor, Chair Gene-Immunotherapy, Regensburg Center for Interventional Immunology, University Regensburg

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.

9:05 New Horizons for Adoptive T-Cell Therapy

Phil Darcy, PhD, Professor, NHMRC Principal Research Fellow, Laboratory Head Cancer Immunotherapy, Peter MacCallum Cancer Centre

One of the immunosuppressive pathways which has largely been ignored is the generation of adenosine by CD73 expressed on tumor cells. In this study, we investigated whether blockade of this pathway could enhance ACT using CAR T cells. The study shows         that dual blockade of adenosine and PD-1 suppressive pathways can potently enhance CAR T-cell therapy and this has significant implications for potentially improving therapeutic outcomes of CAR T-cell therapy for patients.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Problem Solving Roundtable Discussions
Innate Killer Cells for Adoptive Immunotherapy: Advantages & Challenges

Moderator: Mark A. Exley, PhD, Vice President, Cellular Immunology, AgenTus Therapeutics, Inc.

How to Use CAR T Cells Effectively in a Solid Cancer Setting

Moderator: Phil Darcy, PhD, Professor, NHMRC Principal Research Fellow, Laboratory Head Cancer Immunotherapy, Peter MacCallum Cancer Centre

Adoptive T Cell Therapy for Solid Tumor: The Challenges to Face

Moderator: Anna Mondino, PhD, Head, Lymphocyte Activation Unit, Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, DIBIT

11:00 Networking Coffee Break

SAFETY AND POLICY FOR T CELL THERAPY

11:20 Chairperson’s Remarks

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

11:20 Advanced Therapy Delivery from NHS - Clinical Infrastructure Requirements

Jacqueline Barry, PhD, Chief Clinical Officer, Cell and Gene Therapy Catapult

A world-first UK system of Advanced Therapies Treatment Centres (ATTC) operating within the NHS framework and supported by the Cell and Gene Therapy Catapult will address the unique and complex challenges of bringing pioneering cell and gene therapy treatments to patients. The three UK centres comprise the Innovate Manchester Advanced Therapy Centre Hub (iMATCH), the Midlands-Wales Advanced Therapy Treatment Centre (MW-ATTC, comprising Wales, Birmingham and Nottingham) and the Northern Alliance Advanced Therapies Treatment Centre (NAATTC, comprising Scotland, Newcastle and Leeds).

11:50 Strategies for Commercialization and Reimbursement for CAR T-Cell Therapy

James Warburton, Global Program Medical Director, Novartis Pharma AG

12:20 PANEL DISCUSSION: Safety Management of Cytokine Release and Toxicity

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

Panelists: Fiona Thistlethwaite, MB, PhD, Consultant, Medical Oncology, The Christie NHS Foundation Trust

James Warburton, Global Program Medical Director, Novartis Pharma AG

Kirsty Wydenbach, PhD, Deputy Unit Manager, Senior Medical Assessor, Clinical Trials Unit, Medicines and Healthcare Products Regulatory Agency

Additional Panelists to be Announced

• How do we prepare an institution for a multidisciplinary approach to managing gene-modified T-cell therapy-related AEs?
• The role of the new FACT standards for immune effector cells
• Establishment of common CRS management algorithms

12:50 Networking Refreshment Break with Light Snack

THE QUEST FOR OFF-THE-SHELF THERAPEUTIC T CELLS

13:30 Chairperson’s Opening Remarks

Mark A. Exley, PhD, Vice President, Cellular Immunology, AgenTus Therapeutics, Inc.

13:35 Non-Gene Edited Approaches to Allogeneic CAR T-Cell Therapy

Peggy Sotiropoulou, PhD, Director, 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 allogeneic CAR T approach that does not involve gene editing methodologies will be discussed.

14:05 Targeting Cytokines to the Tumor Vasculature to Improve the Therapeutic Efficacy of Adoptive T-Cell Therapy

Anna Mondino, PhD, Head, Lymphocyte Activation Unit, Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, DIBIT

T-cell engineering with T-cell receptors (TCR) or chimeric antigen receptors (CAR) specific for tumor-associated antigens has been employed in anti-tumor adoptive T-cell therapy. Remarkable clinical success has been reached against hematological malignancies. Physical and functional barriers still limit efficacy against solid tumors. Data supporting the beneficial effects of targeting cytokines to the tumor vessels to improve intratumoral T-cell effector representation and function will be discussed.

14:35 Cellular Therapies – Safe, Affordable and Effective Treatment Option

Stefan Scherer, MD, PhD, Chief Medical Officer, Cellectis Inc.

Chimeric antigen receptor (CAR)-redirected T-cells have given rise to long-term durable remissions and remarkable objective response rates in patients with refractory leukemia, raising hopes that a wider application of CAR technology may lead to a new paradigm in cancer treatment. A limitation of the current autologous approach is that CAR T-cells must be manufactured on a "per patient basis". Cellectis has developed a platform for generating chimeric antigen receptor (CAR)-redirected T-cells from third-party healthy donors using transcription activator-like effector nucleases (TALEN®). Nuclease mediated inactivation of the TCR alpha abrogates the potential for T-cells bearing alloreactive TCR's to mediate Graft versus Host Disease (GvHD). Additional gene inactivation events can be incorporated, permitting resistance to lymphodepleting or chemotherapeutic agents, resistance to tumor inhibition or suppression of cross T-cell reactions.  Such allogeneic “off-the-shelf” CAR T-cell products will permit a wider application of CAR technology and potentially lead to a new paradigm in cancer treatment.

15:05 Gene Editing of Stem Cells for Universal SPEAR T-Cell Therapies

Lee Carpenter, PhD, Principal Scientist, Stem Cell Research, Adaptimmune Ltd.

Adoptive T cell therapy using autologous material for CAR and TCR therapies show considerable promise. However, an off-the-shelf product will speed up the time to treat patients and provide a consistent and unlimited source of therapeutic cells. Stem cells are also amenable to genetic modification, allowing them to remain hidden from the immune system for long-term persistence of differentiated T cells expressing enhanced affinity TCRs.

15:35 End of Summit

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