![Winning Strategies for CAR T, TIL and TCR Therapy Winning Strategies for CAR T, TIL and TCR Therapy banner](jpg/track-header_car.jpg)
In the past year, the CAR T-cell therapy field has heated up considerably with two recently approved therapies, Kymriah™ and Yescarta™. Efforts to design CAR, TCR and TILs with greater targeting precision, safety profiles and efficacy are
leading to a new generation of improved products that will continue to propel the field forward. Come to CHI’s Inaugural Winning Strategies for CAR T, TIL and TCR Therapy track at the PEGS Europe Summit to learn engineering updates, clinical
progress and streamlined manufacturing that promise to greatly advance T-cell therapies forward.
Final Agenda
Day 1 | Day 2 | Download Brochure | Interactive Speaker Biographies
Scientific Advisory Board
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London
Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine
WEDNESDAY 14 NOVEMBER
07:45 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London
08:35 T4 Pan-ERB-Targeted CAR T-Cell Immunotherapy of Head and Neck Cancer: Phase I Trial Results
John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s
College London
T4 immunotherapy comprises T-cells that have been engineered to co-express (i) T1E28ζ, a CD28+CD3ζ CAR that engages 8 of 9 ErbB homo- and heterodimers and (ii) 4αβ, a chimeric cytokine receptor consisting of the IL-4Rα ectodomain
coupled to the IL-2Rβ endodomain. To de-risk T4 immunotherapy, a dose-escalation intra-tumoral Phase I clinical trial was commenced in SCCHN patients, without lymphodepletion. An update on the trial will be provided.
09:05 Imaging CAR T-Cell Migration and Activation in Human Tumor Explants
Emmanuel Donnadieu, PhD, Department of Infection, Immunity and Inflammation, Institut Cochin, Université Paris Descartes
Chimeric antigen receptor (CAR) T-cell immunotherapy has demonstrated very promising results in haematological malignancies. However, significant challenges remain to obtain similar results for solid tumors. To attack a tumor, CAR T-cells need to enter
into the malignant tissue, navigate within the tumor environment and then mediate their effector functions to cause destruction of cancer cells. All of these criteria that rely on proper migration of T-cells must be met for a treatment to be effective.
In my presentation, I will describe the approach based on fresh tumor slices that we use to image T-cells and look at their dynamic activities in solid tumors. This approach enabled us to make significant progress in the understanding of how T-cells
are blocked in their migratory activities with the identification of the extracellular matrix and macrophages as having a negative influence on T-cells. We have recently adapted this approach to monitor EGFR CAR T-cell functions in solid tumors. Our
results indicate that the spatial orientation of tumor cells from epithelial origin dictates the migration and activation of CAR T-cells.
09:35 NKG2D CAR T-Cell Therapy: Developing an Autologous and Allogeneic CAR T Approach Exploiting the Targeting Capacity of the Innate Immune System
Alexandre Michaux, PhD, R&D Associate, 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 autologous
approaches and also allogeneic CAR T approaches that do not involve gene editing methodologies and these will be discussed.
10:05 Target Specificity Screening of CAR T-Cells Using Human Cell Microarray Technology
Mark Aspinall-O’Dea, EMEA, Business Development Manager, Retrogenix Limited
Human cell microarray screening enables the discovery of both primary cell surface 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 for antibodies, scFvs and CAR T cells to aid safety assessment and provide key data to support IND submissions.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
11:15 Targeting the Tumour Vasculature with CAR T-Cells
Steven P. Lee, PhD, Senior Cancer Research Fellow and Training Lead for the Birmingham CRUK
Cancer Centre, Institute of Immunology and Immunotherapy, University of Birmingham
To improve CAR T-cell therapy for solid tumours, rather than targeting malignant cells directly, we are developing CARs to target markers on the tumour vasculature. Having identified the C-type lectin CLEC14A to be selectively overexpressed on tumor
vasculature, we have generated CARs targeting this marker that are safe and effective at inhibiting tumour growth in three mouse models of cancer. We are currently developing the approach for a Phase I trial.
11:45 Imaging CAR T-Cells
Sophie Papa, PhD, Senior Lecturer and Honorary Consultant Medical Oncologist, King’s
College London
Clinical translation of CAR/TCR T-cell therapy would be enhanced if we could reliably trace the behavior in vivo of the cell product after infusion. Ideally, this non-invasive assessment of T-cell biodistribution
would utilise a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer. Here we demonstrate the utility of the human sodium iodide symporter for temporal and spatial monitoring
of CAR T-cell behavior.
12:15 Resistance to Chimeric Antigen Receptor T-Cells for Hematological Malignancies
Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, Lymphoma Program,
Division of Hematology and Oncology, Center for Cellular Immunotherapies (CCI), University of Pennsylvania Perelman Center for Advanced Medicine
Anti-CD19 chimeric antigen receptor T cells (CART19) is now an FDA-approved drug for relapsed leukemia and lymphoma. The approval by the FDA of the first adoptive T cell therapy, the UPenn/Novartis CART19 (CTL019), represents a huge achievement for
cancer treatment and paves the way to the use of the CART technology in other cancers and in combination with other agents. However, a significant subset of patients treated with CART19 still does not respond or relapses. In his talk Dr. Ruella
will present novel findings in the mechanism of CART19 resistance and show recent data on the development of CART combination strategies to overcome resistance.
12:45 Preclinical Selection of Optimal TCR Candidates for Cancer Immonotherapy
Claudia Wagner, PhD, Asscociate Director, Immunology, Immatics Biotechnologies GmbH
TCR-based immunotherapy is emerging as promising alternative to CAR-T approaches, especially for solid cancers. Our proprietary TCR platform generates TCRs highly specific for XPRESIDENT®-validated tumor antigens. We use unique information from
the large XPRESIDENT® collection of healthy tissues and tumor biopsies for the selection of efficient and safe TCR candidates.
13:00 Sponsored Presentation (Opportunity Available)
13:15 Luncheon Presentation I Digital to DNA: Using Automation for Rapid Assembly of Synthetic DNA
Kurt Klimpel, Senior Director, Global Product Management, Clinical Solutions, Product Management, SGI-DNA. Inc.
Identifying new CAR T cell therapies requires screening many CAR candidates for optimal biophysical and immunological properties. This process can be streamlined with the BioXp™ 3200 System, an automated genomic workstation that builds DNA libraries
and constructs. In this presentation, we will describe the use of the instrument for building constructs containing specificity-conferring extracellular antibody single-chain variable fragments (scFv) and an accelerated workflow for building CAR
constructs.
13:45 Luncheon Presentation II (Sponsorship Opportunity Available)
14:15 Session Break
14:30 Chairperson’s Remarks
Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine
14:35 KEYNOTE PRESENTATION: The ImmTAC Platform: How Far We Have Come and Where We Are Going
Bent K. Jakobsen, PhD, CSO, Immunocore Ltd.
Immune mobilizing monoclonal TCRs against cancer (ImmTAC™) molecules are a novel class of immunotherapy agent comprised of a soluble T cell receptor (TCR) fused to a T-cell redirecting scFv anti-CD3. ImmTAC molecules offer distinct advantages
over antibody- and cell-based formats, including access to a much larger pool of antigens in a soluble platform. The lead ImmTAC molecule, IMCgp100, has demonstrated encouraging preliminary anti-tumour activity in patients with metastatic uveal
melanoma.
15:05 Genetic Engineering of Therapeutic T-Cells
Hans J. Stauss, MD, PhD, Director & Professor, Tumor Immunology, Infection & Immunity
& Transplantation, Royal Free Hampstead NHS Trust
Effective gene transfer platforms can redirect the specificity of patient T-cells using chimeric antigen receptors (CARs) or T-cell receptors (TCRs). In this presentation, we will demonstrate that optimal TCR expression in engineered T-cells is essential
for optimal antigen-specific function. We will combine TCR transfer with the engineering of T-cell effector function and show that this combination approach provides best cancer immunity in a murine model.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
16:15 Adoptive Cell Therapy-Based on TILs in the Era of Check Point Inhibitors
Marco Donia,
MD, PhD, Staff Physician and Scientist, Medical Oncology, Herlev Hospital
TIL ACT approach can mediate complete and durable responses in 10%-20% of patients with metastatic melanoma, and can also yield clinical responses in other selected types of solid tumors. The presentation will include data on predictive markers for
response, the role of neo-epitopes, immune escape mechanisms, as well as data on TIL ACT in anti-PD1 refractory patients and TIL ACT in combination with check point inhibitors.
16:45 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
We have developed two new techniques that allow rapid determination of the ligand recognised by any ‘orphan’ T-cell clone. These techniques have enabled discovery of novel cancer-associated epitopes that are present on the surface of most
cancers.
17:15 Moderator
Moderator: Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine
Panelists:
Marco Ruella, MD, Assistant Professor of Medicine, Scientific Dir. Lymphoma Program, Division of Hematology and Oncology, Center for Cellular Immunotherapies (CCI), University of Pennsylvania Perelman Center for Advanced Medicine
Marco Donia, MD, PhD, Staff Physician and Scientist, Medical Oncology, Herlev Hospital
Sophie Papa, PhD, Senior Lecturer and Honorary Consultant Medical Oncologist, King’s College London (invited)
17:45 Networking Reception in the Exhibit Hall with Poster Viewing
18:45 Problem-Solving Breakout Discussions (Foyer E&F)
CAR Versus TCR
Moderator: Hans J. Stauss, MD, PhD, Director & Professor, Tumor Immunology, Infection & Immunity & Transplantation, Royal Free Hampstead NHS Trust
- Sensitivity
- Cross-reactivity
- Signalling
- Profile of effector function
- T cell persistence
19:45 End of Day
Day 1 | Day 2 | Download Brochure
THURSDAY 15 NOVEMBER
08:00 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Paul Maciocia, PhD, Clinical Training Fellow/BRC Clinical Lecturer in Haematology, Research Department of Haematology, Faculty of Medical Sciences, University College London
08:35 Applying Reporter Gene Imaging to Assessing T Cell CAR Therapy in Cancer
Tammy L. Kalber, PhD, Principle Research Fellow, Center for Advanced Biomedical Imaging, University College London
09:05 Targeting the T-Cell Receptor β-Chain Constant Region for Immunotherapy of T-Cell Malignancies
Paul Maciocia, PhD, Clinical Training Fellow/BRC Clinical Lecturer in Haematology,
Research Department of Haematology, Faculty of Medical Sciences, University College London
T-cell cancers have a poor prognosis with few effective treatments available. We developed a novel immunotherapy based on targeting T-cell receptor β-chain constant domain 1 (TRBC1) or 2 (TRBC2). While normal T-cells contain both TRBC1+ and TRBC2+
compartments, malignancies are restricted to only one. We engineered anti-TRBC1 CAR T-cells, which killed normal and malignant TRBC1+, but not TRBC2+, T-cells in vitro and in vivo.
Thus, anti-TRBC immunotherapy could eradicate a T-cell cancer while preserving T-cell immunity.
09:35 CAR T-Cells –What’s Next? From Personalized to “Off the Shelf” CARs
Anat Globerson Levin, PhD, Senior Researcher & Immunology
Lab Manager, Immunology Research Lab, Tel-Aviv Sourasky Medical Center
CAR (chimeric antibody receptors) T-cell therapy, pioneered in our lab, is a powerful tool for cancer treatment. This approach has proven very effective in clinical trials in leukemia and lymphoma patients and has recently gained FDA approval to treat
certain types of large B-cell lymphoma. Today, the major challenge in the CAR T-cell field is to prevent ‘off-tumor on-target’ toxicity, namely, the risk of damage to the patient’s healthy tissue which expresses the target antigen
of the selected CAR. Furthermore, the manufacturing of CAR T-cells under GMP is a focal point for this promising therapeutic modality. As personalized therapies, autologous cell-based therapies pose a distinct set of manufacturing challenges.
Protocols must be developed to reduce the number of CAR T-cells needed for a therapeutic effect and treating patients with allogeneic CAR T-cells can facilitate the procedures needed for manufacturing and make CAR T-cell therapy more available
for patients. Here, we will present our solution for these three obstacles. We took advantage of the surface expression of several antigens that are widely expressed on multiple myeloma cells and are poorly expressed by hematopoietic stem cells,
and generated CAR T-cells with dual specificity, expressing two complementary CARs (double CARs) for the specific and effective treatment of MM and to overcome the ‘off-tumor on-target’ toxicity. We will also present the optimization
of CAR T-cell treatments in order to minimize the number of cells administered. Finally, we will present our solution for “Off the Shelf” CARs.
10:05 SELECTED POSTER PRESENTATION: A New T-Cell Signature to Study T-Cell Infiltration of Human Cancers: Prognostic and Predictive Value
Giuseppe Nocentini, MD, PhD, Associate Professor, Medical School, Chair of Pharmacology, Member EASA (Eur Academy Sciences Arts) and EAACI (Eur Academy Allergy Clin Immunol), Department of Medicine, University of Perugia
The poster describes the development by bioinformatic analysis of a new human T-cell signature (signature-H). It comprises 15 genes that are over-expressed at least tenfold in resting and activated T-cells as compared to non-lymphoid tissues and cell
lines. We compared signature-H with published signatures and demonstrated that signature-H shows high sensitivity for evaluating T-cell infiltration in healthy tissues. Among the 32 tumors investigated, based on the expression of signature-H,
5 and 11 tumors were heavily and moderately infiltrated by T-cells, respectively, as compared to healthy tissues (no heavily infiltrated tumors and a lower number of moderately infiltrated tumors were described by the other signatures). We also
tested signature-H in the precision medicine perspective and demonstrated that signature-H works as well as immunohistochemistry methods (the currently accepted standard) for assessing the prognosis of neuroblastoma. Finally, we used a multiparametric
tool that includes T-cell infiltration based on signature-H to predict the response of melanoma to the anti-PD-1 antibody nivolumab and obtained positive preliminary results.
10:20 SELECTED POSTER PRESENTATION: Binders for Challenging Tasks - A High-Throughput DARPin Selection Pipeline
Joana Marinho,
Research Associate, University of Zurich
Obtaining high-quality and reliable affinity reagents remains a major challenge for many scientific projects. Thus, a robust pipeline for high-throughput generation of specific and renewable protein binders is key to enable novel applications. To
optimize the efficiency and capacity of this normally laborious and time-consuming process, our facility established a streamlined pipeline, consisting of high-number parallel Ribosome Display selections [1] and various semi-automated high-throughput
screening and validation assays. We can perform simultaneous selections against 92 targets and subsequently analyze thousands of binders for their binding and biophysical characteristics. Optimized assays allow predictions of the candidates' properties
early in the discovery process, routinely yielding multiple monomeric, high-affinity Designed Ankyrin Repeat Proteins (DARPins) [2] against different epitopes for each processed target.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
11:15 Moderator
G. Jonah Rainey, PhD, CEO, Oriole Biotech, Inc.
- Comparison of efficacy: Approved and pipeline molecules. What is the best clinical endpoint?
- Costimulation: Included as part of the CAR, but what about bispecifics?
- Toxicity: Mechanisms of CRS/cytokine storm and ways to prevent and manage them
- On/off target activation: Runaway CAR T proliferation, off-target effects, and antigen-independent T-cell activation
Panelists:
Sophie Papa, PhD, Senior Lecturer and Honorary Consultant Medical Oncologist, King’s College London
Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, Lymphoma Program, Division of Hematology and Oncology, Center for Cellular Immunotherapies (CCI), University of Pennsylvania Perelman Center for Advanced Medicine
Tariq Ghayur, PhD, Distinguished Research Fellow, Foundational Immunology, AbbVie Bioresearch Center
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
14:00 End of Winning Strategies for CAR T, TIL and TCR Therapy
17:00 Dinner Short Course Registration* (Foyer C)
17:30 – 20:30 Dinner Short Courses
Recommended Short Course*
SC10: Engineering of Bispecific Antibodies - View Detailed Agenda
Nicolas Fischer, PhD, Head, Research, Novimmune SA
Michela Silacci, PhD, Director, Discovery Research, Covagen AG, part of J&J
By attending this interactive workshop, you will learn about the various approaches used for the engineering of bispecific antibodies and bispecific scaffold-based binding proteins. Different technologies will be compared, and examples for
applications of bispecific antibodies in drug development will be presented with a focus on candidates that are currently being evaluated in clinical trials. Opportunities and challenges as well as current trends in the field of bispecific
antibodies will be discussed.
*Separate registration required.
Day 1 | Day 2 | Download Brochure