Original Agenda
We are actively working with our speakers to confirm their availability for the virtual event. Initial response from our speakers has been very positive, and we are optimistic we will have the new programs ready to share here soon.

Winning Strategies for CAR T Therapy, TILs and TCRs track banner

Engineering efforts dedicated to the improvement of the design of CAR, TCR and TIL constructs are enabling a new generation of molecules that are more targeted, manufacturable, and scalable than ever before. Tremendous enthusiasm has emerged around off-the-shelf cancer vaccines and recent progress has illuminated the possibility of a new class of T cell clone that is selective for killing human cancer cells and not harming non-cancerous, healthy cells. Join the lively debate about the present state-of-the-art of adaptive immunity and future of this ground-breaking field.

Wednesday, 11 November

07:45 Registration and Morning Coffee

WINNING STRATEGIES FOR GAMMA DELTA T CELL THERAPY: ADVANCES IN ADOPTIVE AND BISPECIFIC ANTIBODY APPROACHES

08:30

Chairperson's Opening Remarks

Paul Parren, PhD, Executive Vice President & Head, Lava Therapeutics
08:35 BTN3A and BTN2A Are New Immune-Checkpoint Targeting Vg9Vd2 T Cell Functions against Cancer Cells
Daniel Olive, MD, PhD, Head, Tumor Immunology, Marseille Cancer Research Center

Vg9Vd2 T cell activation leads to broad functional activities against tumors. Tumor-infiltrating γδ T cells are the most significant favorable cancer-wide prognostic signature. Anti-tumoral response of Vg9Vd2 T cells requires sensing of phosphoantigens accumulated through binding of butyrophilin 3A(BTN3A) expressed in tumors. We identified butyrophilin 2A (BTN2A) as a requirement for BTN3A-mediated Vg9Vd2 T cell cytotoxicity against cancer cells.

09:05 Bispecific γδ-T Cell Engagers for Cancer Immunotherapy
Hans van der Vliet, MD, PhD, CSO, Lava Therapeutics

Vγ9Vδ2-T cells constitute the largest γδ-T cell subset in human peripheral blood and are powerful anti-tumor immune effector cells that can be identified in many different tumor types. This presentation will discuss bispecific antibodies designed to engage Vγ9Vδ2-T cells and their use for cancer immunotherapy.

09:35 Enhancing CAR T Cell Therapy by Enabling CAR T Cell Interaction with Antigen-Presenting Cells (APCs)
Clare Y. Slaney, PhD, Senior Research Officer, Peter MacCallum Cancer Centre

In the current study, we generated novel bispecific proteins to mediate the interaction between APCs and CAR T cells. We termed these bispecifics “Bispecific Engagers of APCs and T Cells (BEATs)”. CAR T cell proliferation and function was significantly enhanced by BEATs in the presence of APCs in vitro and in vivo. Importantly, murine syngeneic and human xenograft solid tumor growth was significantly inhibited when CAR T cells were administered in combination with BEATs.

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

WINNING STRATEGIES FOR GAMMA DELTA T CELL THERAPY: ADVANCES IN ADOPTIVE AND BISPECIFIC ANTIBODY APPROACHES (CONT.)

11:10

Chairperson's Remarks

René Hoet, PhD, CSO, Oncology, ImCheck Therapeutics
11:15

A Single Cell's Painting of the Landscape of gd T Lymphocytes Infiltrating Human Cancers

Jean-Jacques Fournie, PhD, Research Director, Non Conventional Antigens, INSERM

gd T lymphocytes are usually considered unconventional, infrequent, and redundant to adaptive T lymphocytes. Allied to anticancer activities and versatility however, such hallmarks represent advantages to innovate immunotherapeutic strategies. Currently though, neither extent nor functions of tumor-infiltrating gd T lymphocytes (gd TILs) in cancer patients are known at the single cell level. We will review here these hallmarks as unveiled by the latest progresses in multimodal single cell transcriptomics.

11:45 First-in-Human Applications for Autologous and Allogeneic γδT Cells in Solid and Hematopoietic Cancers
Lawrence Lamb, Jr., PhD, Executive Vice President & CSO, Incysus Therapeutics, Inc.

Drug Resistant Immunotherapy (DRI), a first-in-class approach to solid tumor cancers, is currently undergoing safety evaluation in a Phase I clinical trial. This strategy combines transient chemotherapy-induced upregulation of tumor NKG2DL expression with simultaneous infusion of gene-modified, chemotherapy-resistant expanded/activated γδ T cells. Designed to target multiple tumor stress receptors at the optimal window of tumor vulnerability, DRI has shown significant promise in our initial models of glioblastoma multiforme. A companion Phase I trial of allogeneic γδ T cell therapy as prophylaxis against leukemia recurrence during prolonged immunodeficiency will test the safety and efficacy of allogeneic delivery in the post-transplant setting.

12:15

Advancing Vδ1 T Cells to the Clinic: A Unique Allogeneic Adoptive Cell Therapy Platform

Oliver Nussbaumer, PhD, Founder & Vice President, Immunology, GammaDelta Therapeutics, Ltd.

The treatment of malignancies with adoptive cell therapy is largely limited to patient-derived, autologous alpha beta T cells. This approach comes with challenges (toxicities, relapse, production costs, lack of migration) and a requirement for gene editing to avoid graft vs. host disease in allogeneic settings. In contrast, V delta 1 T cells innately recognise malignant cells, are not MHC-restricted, and facilitate broader immunological responses. Thus, they are an ideal vehicle for immunotherapy.

Benjamin Doranz, PhD, President and CEO, Integral Molecular

Emerging data suggests that approximately 25% of therapeutic MAbs in development are polyspecific and can result in severe or even life-threatening adverse events. We developed the Membrane Proteome Array (MPA) to de-risk MAb safety by specificity testing across an array of 6,000 native membrane proteins. Having tested hundreds of molecules, we will discuss the importance of specificity testing during discovery and case studies of clinical MAb and CAR T safety failures that could have been averted.

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 (Sponsorship Opportunity Available)
14:15 Session Break

ACTIVATING GAMMA DELTA T CELLS

14:30

Chairperson's Remarks

René Hoet, PhD, CSO, Oncology, ImCheck Therapeutics
14:35

Development of a Next-Generation Anti-Cancer Immunotherapy into the Clinic: A Humanized Anti-BTN3A Antibody that Activates Vγ9Vδ2 T Cells

René Hoet, PhD, CSO, Oncology, ImCheck Therapeutics

ImCheck Therapeutics is developing the first activating humanized antibody to butyrophilin3A (BTN3A). ICT01 binds to BTN3A that specifically activates human gamma9delta2 T cells and has entered into Phase I studies in solid and hematological malignancies. Additionally, therapeutic antibodies against multiple novel butyrophilins are currently developed. These novel antibodies have a clearly differentiated mode of action from ICT01 by functional effects on other immune cells critical in the immune responses to tumours. This opens a completely new space clearly different from the current B7/CD28 superfamily targets and has the potential to become the next generation therapeutic immune modulators.

15:05 TEGs: αβT Cells Engineered to Express Defined γδT Cell Receptors
Jürgen Kuball, PhD, Head, Hematology, University Medical Center Utrecht

Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens and are therefore primarily restricted to tumours with high mutational load. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. In this review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing
16:15 Butyrophilin 2A1 Mediates Phosphoantigen Recognition and Tumor Targeting by Gamma Delta T Cells
Adam Uldrich, PhD, Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne

Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs), which respond to phosphoantigens (pAg) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that directly binds to the Vγ9+ TCR γ-chain. We found that BTN2A1 is highly expressed on a variety of cancer tissues and cell lines and associates with BTN3A1, which act together to initiate responses to pAg. This unique mode of MHC-independent T cell activation was essential for γδ T cell cytokine expression as well as γδ T cell-mediated killing of tumor cells. Knockout studies in melanoma cells confirmed the absolute requirement for BTN2A1 and BTN3A1 in this process. While most current immunotherapy approaches rely on (re)-activation of conventional alpha-beta (aß) T cells, this finding creates additional opportunities for the development of γδ T cell-based immunotherapies utilizing a different part of the immune system.

16:45

Harnessing Blood-Derived Gamma Delta T Cells for Cancer Immunotherapy

John Maher, PhD, Consultant & Senior Lecturer, Immunology, Kings College London

Intra-tumoural blood derived gamma delta T cells correlate strongly with superior outcome across a range of cancer types. However, immunotherapy with blood-derived gamma delta T cells has largely proven ineffective. We have found that when these cells are expanded in the presence of TGF-beta, they acquire a fitter, less differentiated phenotype, enabling these cells to elicit improved anti-tumour activity. In this presentation, we will illustrate the anti-tumour activity of TGF-b-supplemented, blood-derived gamma delta T cells across a spectrum of solid and haematological malignancies. Moreover, we will present our experience with CAR targeting of these cells.

17:15 PANEL DISCUSSION :

PANEL DISCUSSION: Comparing and Contrasting Antibody vs. Cellular Approaches

Panel Moderator:
Mihriban Tuna, PhD, MBA, CSO, Adaptate Biotherapeutics Ltd.
Panelists:
Jean-Jacques Fournie, PhD, Research Director, Non Conventional Antigens, INSERM
René Hoet, PhD, CSO, Oncology, ImCheck Therapeutics
Jürgen Kuball, PhD, Head, Hematology, University Medical Center Utrecht
Lawrence Lamb, Jr., PhD, Executive Vice President & CSO, Incysus Therapeutics, Inc.
John Maher, PhD, Consultant & Senior Lecturer, Immunology, Kings College London
Oliver Nussbaumer, PhD, Founder & Vice President, Immunology, GammaDelta Therapeutics, Ltd.
Adam Uldrich, PhD, Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne
17:45 Networking Reception in the Exhibit Hall with Poster Viewing
18:45 Problem Solving Breakout Discussions*

*Topics to be announced.

19:45 End of Day

Thursday, 12 November

08:00 Registration and Morning Coffee

CAR T AND SOLID TUMORS – HOW WE MAKE THE LEAP

08:30

Chairperson's Remarks

John Maher, PhD, Consultant & Senior Lecturer, Immunology, Kings College London
08:35 T Cell Therapy for Solid Tumors
George Coukos, MD, PhD, Director, Oncology, Ludwig Institute for Cancer Research

Private neoantigens derived from tumor mutations are immunogenic and attractive targets for tailored T-cell immunotherapies. Our latest efforts aim at an in-depth dissection of neoantigen-specific, infiltrating and circulating T-cells — including their frequency, functionality, clonotypic analysis — in patients receiving personalized immunotherapies, and their association with clinical response. Tracking the origin, expansion, and persistence of neoantigen clonotypes upon infusion helps us understand how to better mobilize T-cell reactivities against the patient’s mutanome.

09:05 Next-Generation CAR T Cells for the Treatment of Solid Tumors
Sònia Guedan, PhD, Principal Investigator, Hematology & Oncology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

Despite the remarkable results of CAR T cells in patients with hematologic malignancies, the success of CAR T cells in treating patients with solid tumors has been poor. A major obstacle for the field is the limited ability of CAR T cells to persist and maintain their functions in the tumour microenvironment. New approaches to enhance the persistence and efficacy of CAR T  cells will be presented, focusing on the treatment of solid tumors. 

09:35 Toward Targeting Pancreatic Cancer with CAR T Cells
John Marshall, PhD, Professor & Centre Leader, Tumour Biology, Barts Cancer Institute, Queen Mary University of London

Pancreatic Ductal Adenocarcinoma remains the worst possible cancer diagnosis. With a median survival of 6 months, a 5 year survival of 4% and the expected likelihood that it with be second largest cause of death from cancer by 2030, this is a disease desperate for novel therapies. We chose PDAC to develop CAR T cell therapy for even though it is an especially difficult solid cancer to treat owing to its being highly desmoplastic, poorly vascularised and extremely immunosuppressive. Any significant success in PDAC would translate immediately to other solid cancer. To address the role of immunosuppression we have generated a novel mouse PDAC model that better reflects the human PDAC disease and allows us to develop improved syngeneic studies. To that end we have generated both human and mouse CAR T cells and will describe our progress and pitfalls for both.  Specifically I will outline our recent data on targeting different potential PDAC-selective antigens including VAR2, Agr2 and avb6.

Sebastian Bunk, Senior Director, Immunology, Immatics Biotechnologies GmbH
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Computationally Designed STOP-CAR Disrupted by Small Molecule Confers On-Command Regulation of T Cell Therapy
Bruno Correia, PhD, Assistant Professor, Laboratory of Protein Design & Immunoengineering, University of Lausanne

Chimeric antigen receptor (CAR) T cells have enabled remarkable advances in cancer therapy, but unexpected toxicity and other adverse side effects remain an important issue. To engineer safety, we computationally designed a synthetic chemically disruptable heterodimer (CDH) featuring a high-affinity protein interface with minimal amino acid deviation from wild-type, which self-assembles but can be disrupted by a small molecule. The CDH was incorporated into a synthetic heterodimer receptor, dubbed STOP-CAR, featuring an antigen-recognition chain and a CD3z- and CD28-containing endodomain signaling chain. STOP-CAR-T cells exhibited similar activity to classic second-generation (2G) CAR-T cells in vitro and in vivo against tumors, while timed administration of the small-molecule drug disruptor dynamically inactivated the STOP-CAR-T cells. We propose that STOP-CARs hold important clinical promise, and our work highlights the potential for rational, structure-based design to implement novel, controllable elements into synthetic cellular therapies.

11:45 Arming CAR T Cells for Metabolic Competition in the Tumour Microenvironment
Sophie Papa, PhD, Reader and Honorary Consultant Medical Oncologist, King’s College London

Metabolic competition in the tumour microenvironment is a limiting factor in cancer immune therapy. T cell efficacy and phenotypic changes are dependent on shifts in metabolic pathways within individual cells. I will explore approaches to target a putative tumour associated antigen is a key role in metabolic solute availability as well as methods to adapt CAR T cells to be armed to better manage competitive cancer microenvironment.

Nancy Lopez-Anton, PhD, Antibody Discovery Team, OXGENE

Our novel Self-Labelling Integral Membrane (SLIM) display technology addresses the limitations of traditional mammalian display. It involves co-expression of large antibody libraries in a population of mammalian cells, which each display the target membrane protein on the cell surface. We’ve successfully identified a panel of novel scFv binders to Epithelial Cell Adhesion Molecule (EpCAM). We further demonstrate that these antibodies can kill EpCAM positive cells when used as a targeting domain on CAR T cells.

12:45 Luncheon Presentation II (Sponsorship Opportunity Available)
13:15 Dessert Break in the Exhibit Hall with Poster Viewing
14:00 Close of Winning Strategies for CAR T, TILs and TCRs
17:00 Dinner Short Course Registration
17:30 Recommended Dinner Short Course*
SC8: CAR T Cell Therapy from A-Z

*Separate registration required. See short course page for details.