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
Day 1 | Day 2 | Download Brochure
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
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 dCODE T-cell Immunity
Liselotte Brix, PhD, CSO & COO, Immudex
Identification of disease-specific T-cells and their cognate T-cell receptors (TCRs) is key to the development of immunotherapies. The extreme diversity of the TCR repertoire represents a major challenge to the characterization of T-cell immunity.
This talk presents new technologies within T-cell immunomonitoring allowing a new understanding of cancer immunology.
9:55 Sponsored Presentation (Opportunity Available)
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
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) or Enjoy Lunch on Your Own
12:50 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing
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 Tune the Drivers of Immune Cell Potency, Fate and Fitness
Alex Liversage, PhD, Agilent Cell Analysis Division, Agilent Technologies
Immunotherapy is changing the landscape of cancer treatment, but most available tools are adapted and not purpose-built for this cell-centric workflow. Agilent Technologies is dedicated to supporting these next-generation therapies, providing
key technologies to measure immune cell function, enabling researchers to achieve the necessary level of therapeutic potency and safety.
15:10 Sponsored Presentation (Opportunity Available)
15:25 Refreshment Break in the Exhibit Hall with Poster Viewing
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 Breakout Discussions (See complete list of Problem-Solving Breakout Discussion)
Novel Strategies for Overcoming Antigen Heterogeneity for Enhancing CAR T Cell Efficacy
Moderator: Phil Darcy, PhD, Professor, NHMRC Principal Research Fellow, Laboratory Head Cancer Immunotherapy, Peter MacCallum Cancer Centre
- Preclinical work using armored CAR T cells. Discussion of different cytokines that have been used in this format.
- Discussion of strategy using dual expressing CAR T cells to overcome antigen heterogeneity.
- Translational feasibility of these new approaches
Are Innate Immune Cells More Tolerant of the Tumour Microenvironment than T Cells?
Moderator: Mark Lowdell, PhD, Director, Centre for Cell, Gene & Tissue Therapeutics, RFH; Professor, Cell & Tissue Therapy, University College London
- Effects of hypoxia on NK, CAR-NK, Gamma delta T cell and monocyte activation
- Direct and indirect effects of Treg on NK function
- Role of MDSC in innate immune suppression in the TME
18:05 Welcome Reception in the Exhibit Hall with Poster Viewing
19:05 Close of Day
Day 1 | Day 2 | Download Brochure
WEDNESDAY 11 MARCH
7:45 Registration and Morning Coffee
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
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
Day 1 | Day 2 | Download Brochure