Cambridge Healthtech Institute’s 5th Annual

CARs, TILs, TCRs

Effective Strategies Beyond Conventional Platforms

10-11 March, 2020

 

The therapeutic potential of adoptive cell therapy was first acknowledged a couple of decades ago, but it was only recently that we transformed adoptive 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 cell therapy, there is still much to be done to reach its full potential including other novel cell therapies beyond T cells. Cambridge Healthtech Institute’s 5th Annual CARs, TILs, TCRs 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 and non-T cell therapies.

Final Agenda

MONDAY 9 MARCH

Recommended Short Course*

SC2: Next-Generation Immunotherapies - LEARN MORE

Stephen Beers, PhD, Professor, Immunology and Immunotherapy, Cancer Immunology, University of Southampton Faculty of Medicine

Eric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals

Dario Neri, PhD, Professor, Biomacromolecules, Swiss Federal Institute of Technology (ETH Zürich), Switzerland

John Maher, MD, PhD, Consultant and Senior Lecturer, Immunology, Cancer Studies, King’s College London

Sophia N. Karagiannis, BA, MS, PhD, Professor, Translational Cancer Immunology and Immunotherapy, St. John’s Institute of Dermatology, Basic & Medical Biosciences, King’s College London

*Separate registration required.

TUESDAY 10 MARCH

7:30 Registration and Morning Coffee


OPENING KEYNOTE SESSION

8:30 Organizer’s Welcome Remarks

Ngoc ‘Emily’ Le, PhD, Conference Producer, Cambridge Healthtech Institute

8:35 Chairperson’s Remarks

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

8:40 TILs in Solid Tumors: Lessons from Ovarian Cancer

George Coukos, Full Professor and Director, Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL); Director, Lausanne Branch, Ludwig Institute of Cancer Research Chief, Service of Immuno-Oncology, CHUV

Our work has sought to answer the following key questions: a) whether ovarian TILs are tumor-specific; b) if so, what are the relevant antigens recognized by TILs; c) whether the PD-1/PD-L1 pathway is relevant; d) if so, what are the mechanisms underlying response to PD-1 blockade; and finally e) what mechanisms govern TIL recruitment and engraftment. Therapeutic approaches to achieve effective immunotherapy in ovarian cancer will be discussed, including combination checkpoint blockade, adoptive T cell therapy and new rational combinations.

9:10 CARs and Armored CARs

Renier Brentjens, MD, PhD, Director, Cellular Therapeutics Center, Memorial Sloan-Kettering Cancer Center; Professor, Pharmacology, Weill Cornell Graduate School of Medical Sciences

Based on currently updated clinical outcomes, we have achieved >85% CR rates in adult patients with relapsed B-ALL treated with CD19 targeted CAR T cells which far exceed historical expectations. Further, by deep sequencing analysis, most treated patients were MRD- after CAR T cell therapy. Significantly, remissions were observed in both patients with overt morphological residual disease at the time of therapy as well as in patients with only residual MRD+ disease. To this end, we will present novel data on the next generation of CAR T cells, termed “armored CARs” further genetically designed to overcome an immune-suppressive tumor microenvironment through further genetic modification of CAR T cells.

9:40 Presentation to be Announced

9:55 Sponsored Presentation (Opportunity Available)

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

NEW DEVELOPMENTS IN TILs AND TCRs

10:50 Chairperson’s Remarks

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

10:50 TIL – A Blueprint for Adoptive Cell Therapy in Solid Tumours

Robert Hawkins, MB BS, MRCP, PhD, FRCP, CEO, Immetacyte Ltd.; Honorary Professor, Medical Oncology, University of Manchester

This talk will address the activity of TIL in the checkpoint therapy era and manufacturing advances to facilitate commercial development. It will also discuss developments in engineered TIL to enhance the efficacy and the use of single cell analysis to assess the importance of individual TCR clones.

11:20 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

Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumour-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining the dominant tumour-reactive T cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted T cell targets that are expressed by many other tumour types.

11:50 Adoptive Therapy: What Are Determinants of Safety and Response of Anti-Tumor CD8 T Cells?

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

To further develop adoptive T cell therapy with engineered T cells, it is imperative to understand and predict safety and efficacy of these cells. We will present critical determinants of anti-tumor CD8 T cell behaviour, such as antigen/TCR as well as intra-tumoral CD8 T cell evasion, in light of a scheduled and upcoming TCR T cell trials at Erasmus MC and discuss how these determinants are expected to affect clinical trial outcomes.

12:20 Luncheon Presentation (Sponsorship Opportunity Available)

12:50 Session Break

ENGINEERING NON-T CELLS: STEM CELLS, MACROPHAGES AND NK CELLS

13:20 Chairperson’s Remarks

Robert Hawkins, MB BS, MRCP, PhD, FRCP, CEO, Immetacyte Ltd; Honorary Professor, Medical Oncology, University of Manchester

13:25 Creating Off-the-Shelf Therapies from Stem Cells

Jo Brewer, PhD, Vice President, Allogeneic Research, AdaptImmune

Adoptive T cell therapy using autologous material for CAR and TCR therapies have shown considerable progress; however, an allogeneic, or off-the-shelf, product would speed up the time to treatment and make cell therapy more widely accessible to patients. Stem cells are amenable to genetic modification and could provide a platform for generating consistent and, theoretically, unlimited source of therapeutic immune cells.

13:55 CAR Macrophage Immunotherapy: A New Frontier for Innate Immunity

Michael Klichinsky, PharmD, PhD, Co-Founder, Vice President, Discovery, Carisma Therapeutics

Our approach can overcome the hurdles of cell therapy in the treatment of solid tumors by modulating the tumor microenvironment (TME) through macrophages with key characteristics: recruitment and access to the solid tumor TME, ability to survive in the hostile solid tumor milieu, maintenance of an anti-tumor phenotype in the presence of immunosuppressive factors, capacity to selectively destroy cancer cells, and activation of an adaptive immune response by presenting engulfed tumor material.

14:25 What Do Tumor Cells Do to NK Cells? – Harnessing the Tumor-NK Interaction for Clinical Benefit

Mark Lowdell, PhD, Director, Centre for Cell, Gene & Tissue Therapeutics, RFH; Professor, Cell & Tissue Therapy, University College London

I will discuss how relapsed cancer cells evade natural killer (NK) cells, and how priming NK cells could effectively kill these cancer cells.

14:55 Sponsored Presentation (Opportunity Available)

15:25 Refreshment Break in the Exhibit Hall with Poster Viewing

NEW ENGINEERING APPROACHES FOR CARs

16:05 Chairperson’s Remarks

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

16:05 Flt3l Armored Car T Cells Enhance Endogenous Antitumor Responses in Solid Cancers

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

We engineered T cells to secrete Flt3L, a dendritic cell (DC) growth factor. Flt3L secreting T cells expanded intratumoral CD103+ DCs, leading to increased infiltration of endogenous T cells. Importantly, combination of Flt3L secreting T cells with immune agonists polyinosinic:polycytidylic acid (pIC) and anti-4-1BB antibody significantly inhibited tumor growth and induced epitope spreading in solid tumor models of both TCR and CAR-engineered T cell therapy. Our data indicate that enhancing endogenous immune responses by augmenting intratumoral DC activation is a promising strategy to overcome antigen-negative tumor escape during AC.

16:35 Dynamic Profiling of Antitumor Activity of CAR T Cells on Micropatterned Tumor Arrays

Daniel Irimia, MD, PhD, Associate Professor, Surgery, Harvard Medical School, Massachusetts General Hospital, USA

We will present a high-throughput, high-content platform to quantify the performance of CAR T cells during their traffic towards tumor-cell islands and subsequent killing of tumor cells. The technique provides insights into the collective actions of CAR T cells at levels of detail that are not available through any other current techniques.

17:05 Problem Solving Roundtable Discussions

18:05 Welcome Reception in the Exhibit Hall with Poster Viewing

19:05 Close of Day

WEDNESDAY 11 MARCH

7:45 Registration and Morning Coffee

NEW ENGINEERING APPROACHES FOR CARs (CONT.)

8:30 Chairperson’s Remarks

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

8:35 CARs, Trucks, and Beyond: Novel CAR Formats

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 Exploiting the Nkg2d Receptor for Autologous and Allogeneic Car T Cell Therapy of Cancer

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

Natural Killer Group 2D (NKG2D) is a receptor that binds to eight ligands that are over-expressed in a wide range of cancers. Consequently, forming a chimeric antigen receptor based upon NKG2D could provide a means to generically target T cells against solid cancer and hematological malignancies. Ongoing clinical trials have documented a good safety profile and initial evidence of clinical activity in the autologous setting. In parallel, the NKG2D CAR is also being explored in allogeneic approaches, with the latest results of these trials to be discussed.

9:35 Hypoxia-Sensing CAR T Cells for the Treatment of Solid Tumours

James Arnold, PhD, Professor, Cancer Cell Biology and Imaging, Kings College London

Several hurdles remain for utilising T cells expressing chimeric antigen receptors (CARs) against solid tumours. One major hurdle is on-target off-tumour activation which can result in treatment-limiting toxicity. We created a hypoxia-sensing CAR T cell which achieves selective expression of a pan-ErbB-targeted CAR within a solid tumour and provides anti-tumour efficacy without off-tumour toxicity in a murine xenograft model.

10:05 Tandem CD19-CD20-Redirected CAR T in Treatment of r/r NHL

Weidong Han, PhD, Professor, Biotherapeutic, Chinese PLA General Hospital, Beijing, China

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

10:45 Solutions-Focused Speed Networking in the Exhibit Hall

PLENARY KEYNOTE SESSION

11:15 Organizer’s Remarks

Ngoc ‘Emily’ Le, PhD, Conference Producer, Cambridge Healthtech Institute

11:20 Chairperson’s Remarks

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

11:30 Strategies to Improve Antitumor Efficacy of Genetically Engineered T Cells

Stanley Riddell, MD, Scientific Director, Clinical Research, Fred Hutchinson Cancer Research Center; Professor, University of Washington School of Medicine

Immune cells can be readily genetically modified to express natural tumor targeting antigen receptors or synthetic chimeric antigen receptors (CARs) that activate immune cell signaling pathways to result in destruction of tumor cells expressing the relevant target molecule. The presentation will discuss advances in our understanding of receptor signaling and the development of strategies that combine therapeutic agents to improve efficacy and safely extend the spectrum of cancers that can be treated with cell therapies.

12:00 PD-1 Antibodies Are Transforming Cancer Treatment

Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme

PD-1 antibodies have shown significant activity as monotherapy across multiple cancer types and lines of therapy. Precision medicine tools have been used to identify subjects most likely to respond to PD-1 antibody monotherapy, to provide insight to potential resistance mechanisms, and to inform combination therapies. A number of these combinations have demonstrated significant activity in additional tumor types and lines of therapy.

12:30 Close of CARs, TILs, TCRs

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