Cambridge Healthtech Institute’s Third Annual
Adoptive T Cell Therapy
Delivering CAR, TCR, and TIL from Research to Reality
September 1-2, 2016 | Marriott Long Wharf | Boston, MA
Greater understanding of T cell biology as well as promising patient outcomes have led to immunotherapies accelerating at an unprecedented pace. With multiple engineered receptors making an impact, many biotech and pharma companies are already entering clinical trials in a race to get to market. However, with the end goal being the same – improved patient outcomes – there is still work to be done. Cambridge Healthtech Institute’s Third Annual Adoptive T Cell Therapy event will focus on the steps needed to deliver CAR, TCR, and TIL therapies to the patient. New and emerging receptors including Tregs and NK cells will also be explored. Special focus will be given to target discovery methods and approaches. Overall, this event will address clinical progress, case studies, and critical components to make adoptive T cell therapy work.
Final Agenda
THURSDAY, SEPTEMBER 1
7:45 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
Adrian Bot, M.D., Ph.D., Vice President, Translational Sciences, R&D, Kite Pharma Inc.
8:30 KEYNOTE PRESENTATION: New Approaches to Overcome Tumor Immune Suppression for T-Cell Therapy
Laszlo Radvanyi, Ph.D., Senior Vice President and Head, Immuno-Oncology Translational Innovation Platform (TIP), EMD Serono
Adoptive T-cell transfer therapies have made tremendous progress for treating cancer, with successes emerging especially in hematologic malignancies. Although, these cell therapies offer new ways of genetically reprogramming T cells through altered specificities and redirecting T-cell signaling pathways, immune suppressive mechanisms in the tumor microenvironment, such as PD-1-PD-L1 axis, TGF-beta, and an insufficient Th1 response, still raise great challenges to success in solid tumors. Some key agents aimed at overcoming these issues being developed at EMD Serono will be presented.
9:00 Engineering Better T Cells
Daniel Williams, Head, UK Research Operations, Adaptimmune
Adaptimmune is a clinical-stage biopharmaceutical company developing engineered TCRs for adoptive T cell therapy. Engineering TCRs specific for tumor antigens which are self-antigens, requires balancing the need for increasing affinity to the target peptide to allow recognition of immune-selected tumors, with the risk of cross-reactivity, which increases at higher affinities. Target identification and validation, together with a broad and robust preclinical safety testing strategy are critical in the development of safe and efficacious affinity-enhanced TCRs.
9:30 Development of an Anti-BCMA Specific CAR with Potent Anti-Multiple Myeloma Activity
Richard A. Morgan, Vice President, Immunotherapy, bluebird bio
B cell maturation antigen (BCMA) is expressed on most multiple myeloma (MM) cells, yet normal tissue expression is limited to plasma and some B cells. Here we demonstrate that a potent, antigen-dependent, memory-like BCMA CAR T cells can be produced with a scalable manufacturing process that mediated robust tumor regressions in animal models. A Phase I clinical trial to test this approach in patients with relapse refractor MM is underway.
10:00 Coffee Break with Exhibit and Poster Viewing
10:45 CD19 as a Prototypic B Cell Lineage Target for CAR T Cells
Adrian Bot, M.D., Ph.D., Vice President, Translational Sciences, R&D, Kite Pharma Inc.
Anti-CD19 CAR T cells could be the first marketed products in this space. Prolonged B cell deficiency may not be desirable since B cells are required to combat major pathogens. Product candidates capable to mediate rapid and profound tumor debulking, can yield durable clinical responses without persisting B cell deficiency. Novel evidence will be presented, linking product characteristics, conditioning, and biomarkers, to the clinical outcome afforded by CAR T cells.
11:15 CAR-T Cells for Hematological Malignancies: Exploring Alternative Targets
Gianpietro Dotti, M.D., Professor, Microbiology and Immunology, University of North Carolina
Adoptive transfer of CD19-specific CAR-T cells showed remarkable anti-tumor activity in patients with B-cell derived acute lymphoblastic leukemia and lymphomas. Alternative targets have been explored in Phase I studies in hematological malignancies. Specifically, in the effort to reduce the B cell aplasia associated with effective and long-term persisting CD19-specific CAR T cells, we implemented at Baylor College of Medicine a Phase I study with CAR-T cells targeting the k-light chain of human immunoglobulin to selectively eliminate k+ tumors whilst sparing normal l+ B lymphocytes. To target Hodgkin’s Lymphoma and other CD30+ lymphomas, we also implemented a Phase I study with CAR-T cells targeting the CD30 antigen. Outcome of these studies and future directions will be reported.
11:45 PANEL: CAR T Cell Therapy: Target Antigen Discovery and Clinical Translation
Panelists: Adrian Bot, M.D., Ph.D., Vice President, Translational Sciences, R&D, Kite Pharma Inc.
Gianpietro Dotti, M.D., Professor, Microbiology and Immunology, University of North Carolina
Richard A. Morgan, Vice President, Immunotherapy, bluebird bio
- Market potential of anti-CD19 CAR T Cells
- The latest clinical results
- Scalability and manufacturing challenges
- Future directions for CAR therapies
12:15 pm Sponsored Presentations (Opportunities Available)
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
2:00 Chairperson’s Remarks
Adrian Bot, M.D., Ph.D., Vice President, Translational Sciences, R&D, Kite Pharma Inc.
2:05 Human Papillomavirus (HPV)-Targeted T Cells for HPV-Associated Cancers
Christian S. Hinrichs, M.D., Investigator, Experimental Transplantation and Immunology Branch, Lasker Clinical Research Scholar, NIH
Human papillomavirus (HPV) causes cancers of the uterine cervix, oropharynx, anus, vulva, vagina and penis. These cancers express the HPV E6 and E7 oncoproteins, which are attractive immunotherapeutic targets. Recent work has sought to target these antigens using tumor-infiltrating lymphocytes and genetically engineered T cells.
2:35 XPRESIDENT®-Guided Target Identification and Profiling of On-and Off-Target Toxicity for Safer Adoptive Cell Therapy
Steffen Walter, Ph.D., CSO, Immatics Biotechnologies GmbH
A major constraint for the broad and safe application of Adoptive Cellular Therapy is the limited number of validated tumor targets and TCRs. We used a proprietary target discovery engine (XPRESIDENT®) combining highly sensitive quantitative mass spectrometry, transcriptomics, immunology and bioinformatics to characterize the immunopeptidome directly on human normal and tumor tissues. We show how this approach can be used to predict on- and off-target toxicities in TCR-based immunotherapies.
3:05 Engineering Designer T Cells for Immunotherapy
Wolfgang Uckert, Associate Professor, Department of Cell Biology and Gene Therapy, Humboldt University Berlin
Successful immunotherapy using T cell receptor (TCR) gene-modified T cells to treat cancer, viral infections or autoimmune diseases is depending on the careful selection of: (i) the target antigen, (ii) a TCR with optimal affinity, (iii) an efficient gene delivery system, and (iv) a safety switch to interrupt therapy in case of severe adverse side effects. Examples of these different areas to generate designer T cells for successful TCR gene therapy are given and discussed.
3:35 Refreshment Break
4:05 KEYNOTE PRESENTATION: A COMPARISON OF TCRS AND CARS: SENSITIVITIES AND SPECIFICITIES
David M. Kranz, Phillip A. Sharp Professor, Biochemistry, University of Illinois, Urbana-Champaign
T cells, via their T-cell receptors (TCRs), evolved to target intracellular peptides as low-density, cell-surface complexes with MHC products. Synthetic constructs known as chimeric antigen receptors (CARs) contain an anti-tumor antigen scFv and recognize higher density antigens. We have designed high-affinity human TCRs in conventional heterodimer format and in CAR-like formats to directly compare features of both systems. These features include T cell surface levels, antigen sensitivities and other properties.
4:35 PANEL: Designing T Cells for Immunotherapies
Panelists: Christian S. Hinrichs, M.D., Investigator, Experimental Transplantation and Immunology Branch, Lasker Clinical Research Scholar, NIH
Steffen Walter, Ph.D., CSO, Immatics Biotechnologies GmbH
Wolfgang Uckert, Ph.D., Associate Professor, Cell Biology and Gene Therapy, Humboldt University Berlin
David M. Kranz, Phillip A. Sharp Professor, Biochemistry, Biochemistry, University of Illinois
- Strategies for antigen selection and targeting
- Increasing sensitivity and specificities
- Utilizing efficient gene delivery systems
- Dealing with toxicities
5:35 End of Day
5:05 Dinner Short Course Registration
FRIDAY, SEPTEMBER 2
8:00 am Morning Coffee
8:25 Chairperson’s Opening Remarks
Jonathan Gilbert, Director, Strategic Scientific Partnerships, SQZ Biotech
8:30 Vector-Free Engineering of Immune Cells for Enhanced Antigen Presentation
Jonathan Gilbert, Director, Strategic Scientific Partnerships, SQZ Biotech
Robust engineering of immune cell function is critical to realizing the therapeutic potential of cell therapies in cancer. Our vector-free CellSqueeze technology has demonstrated novel capabilities in diverse areas including engineering antigen presentation to drive powerful and significant T-cell responses. We will present recent developments in our cell-based immunotherapy programs aimed at using patient-derived antigens to target a variety of cancer indications, including solid tumors.
9:00 Design of a Highly Efficacious CAR Targeting Mesothelin in Solid Tumors
Boris Engels, Ph.D., Investigator, Exploratory Immuno-Oncology, Novartis Institutes for Biomedical Research
The treatment of solid tumors with CAR T cells remains challenging. We describe the design of a human CAR targeting mesothelin, a tumor associated antigen overexpressed in many cancers. A pooled screen identified scFvs, which show enhanced efficacy, superior to the CARs currently used in the clinic. We performed in-depth characterization of the scFvs and CARs to gain insight into structure-activity relationships, which may influence CAR efficacy and future design.
9:30 Overcoming CAR T Cell Checkpoint Blockade in Solid Tumors
Prasad S. Adusumilli, M.D., FACS, FCCP, Deputy Chief, Translational and Clinical Research, Thoracic Surgery; Associate Attending, Thoracic Surgery; Member, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center
CAR T-cell therapy for solid tumors is prone to the checkpoint blockade inhibition similar to innate tumor-infiltrating lymphocytes. Strategies to overcome this ‘Adaptive Resistance’ of infused CAR T cells can promote their anti-tumor efficacy and functional persistence. Understanding solid tumor type-specific immune microenvironment can guide both cell-intrinsic and extrinsic strategies that can modulate the solid tumor microenvironment in addition to promoting CAR T-cell efficiency.
10:00 Coffee Break
10:30 Challenges and Opportunities for Scale-up of CAR T Cells
Máire Quigley, Research Investigator I, Cell and Gene Therapies Unit, Novartis
The response rates of autologous CAR T cell therapies in early clinical trials give hope that these treatments can be developed and widely distributed to patients with unmet need. To successfully evolve from small scale production to commercial manufacturing, multiple challenges must be overcome. Lessons learned from the process scale up of CD19 CAR T cell production will be discussed.
11:00 Cell Therapy: Quality and Good Manufacturing Practices
Yeong “Christopher” Choi, Ph.D., Director, TCPF and Assistant Professor, Oncology, Center for Immunotherapy, Roswell Park Cancer Institute
To bring ground breaking new cell therapies into the clinic, a massive amount of infrastructure is needed. One of the key components is a drug manufacturing facility, which is compliant with US FDA GMP regulations. One of the major challenges of operating a cell therapy cGMP facility, is maintaining a robust Quality Management System. Fortunately, there are a number of voluntary accrediting organizations to promote excellence in the laboratory.
11:30 Manufacturing of Cellectis’ Allogeneic UCART Product Candidates
Arjan Roozen, Vice President, GMP Solutions & Manufacturing, Cellectis
This talk will provide an introduction of the concept of Cellectis’ allogeneic UCART product candidates and our technological platform. It will describe and explain the challenges during the process of bringing allogeneic UCART product candidates from R&D development phase to the GMP manufacturing phase, in order to have CTM (clinical trial material) available for clinical studies, and afterwards to plan commercial manufacturing of Cellectis’ allogeneic UCART GMP cellular gene therapy products.
12:00 pm Close of Adoptive T Cell Therapy