Cambridge Healthtech Institute’s 4th Annual
Adoptive T Cell Therapy
Delivering CAR, TCR, and TIL from Research to Reality
August 29 - 30, 2017 | Sheraton Boston | 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 Fourth Annual Adoptive T Cell Therapy event will focus on the steps needed to deliver CAR, TCR, and TIL therapies to the patient by examining emerging science, autologous immune cell products, and allogenic immune cell products. Overall, this event will address clinical progress, case studies, and critical components to make adoptive T cell therapy work.
Final Agenda
TUESDAY, AUGUST 29
12:00 pm Registration
1:15 Chairperson’s Opening Remarks
Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics
1:20 Building Better T Cell Therapies: The Power of Molecular Profiling
Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics
Chimeric antigen receptor (CAR)-T cells are a promising new modality for cancer immunotherapy and many variants are rapidly being developed across the immuno-oncology space for haematological and solid tumor malignancies. The field has displayed enormous promise, however the rules governing which attributes drive efficacy are still being learned. Here, we present early insights from transcriptomic and epigenetic profiling of CAR-T cells describing how cell state may play an important role.
1:50 Tricked-Out Cars, the Next Generation of CAR T Cells
Richard Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio
Genetically-engineered CAR T cells are designed to supplement a patient’s immune system and can be further engineered to survive and overcome immune evasion mechanisms employed by tumors. We found that addition of a PI3-kinase inhibitor during manufacturing enriched for memory-like CAR T cells without complicated cell sorting procedures. These methodologies, combined with synthetic biology and gene editing, can be considered for the further development of CAR T cell technology.
2:20 SPEAR T Cells for Solid Tumor Therapy
Mark Dudley, Ph.D., Senior Vice President, Bioprocessing, Adaptimmune
Adoptive cell transfer with gene modified T lymphocytes is effective for some advanced cancer indications. Specific peptide engineered antigen receptor (SPEAR) T cells that recognize the NY-ESO-1 cancer-testes antigen have shown promise in early phase trials for melanoma, multiple myeloma, and synovial sarcoma. Combination therapies and product improvements are being explored, and a registration trial is planned. Numerous tumor antigen candidates predicted from proteomic and HTS analysis of tumor specimen NAS have been used to generate new SPEAR T cells. T cells targeting MAGE-A10, MAGE-A4, and AFP are approved for initial evaluation in clinical trials in new solid tumor indications in 2017. A robust manufacturing platform that generates multiple SPEAR products for exploratory registration studies will be discussed. Challenges in scaling out successful autologous cell therapies and opportunities for implementing automation and improving T cell products will be assessed.
2:50 The Generation of Lentiviral Vector-Modified CAR-T Cells Using an Automated Process
Boro Dropulic, Ph.D., General Manager and CSO, Lentigen Technology, Inc.
Participants will learn about: 1) How Lentiviral vectors are a proven robust technology to genetically modify cells 2) The Development of a large-scale lentiviral vector manufacturing process using a chemically defined, serum free suspension bioreactors 3) How automation using the CliniMACS Prodigy is a robust and cost effective method to generate patient specific CAR-T cells 4) The design and testing of CAR constructs - factors that influence in vivo efficacy 5) How automation provides options for the manufacture of CAR-T cell products: Centralized vs Decentralized models.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 PLENARY KEYNOTE SESSION
4:00 Regulatory and Scientific Considerations for Cancer Vaccines and Adoptive Cellular Immunotherapy
Graeme E. Price, Ph.D., Research Microbiologist, Gene Transfer & Immunogenicity, FDA CBER
Cell and Gene therapy including therapeutic vaccines and cellular immunotherapy products are evaluated at FDA’s Center for Biologics Evaluation and Research in the Office of Tissues and Advanced Therapies (OTAT) previously known as Office of Cellular, Tissue and Gene Therapies. I will discuss current general regulatory and scientific considerations in the regulation of therapeutic cancer vaccines and cellular immunotherapy. In addition, research activities in OTAT will be summarized.
4:45 Market Access and Reimbursement for Immuno-Oncology Drugs in Today’s Healthcare System
Gergana Zlateva, Ph.D., Vice President, Payer Insights and Access, Oncology, Pfizer
Now that immunotherapies have hit the market, with the promise of more to come, the healthcare system will need to establish standards for cost and reimbursement of immuno-oncology agents. This talk will address how the healthcare marketplace can prepare for the adoption of novel pricing and reimbursement models to increase patient access to immunotherapies. Establishing the value of IO therapies to payers and HTAs will also be addressed in the context of pricing and evidence generation.
Click here for keynote biographies
5:30 Welcome Reception in the Exhibit Hall with Poster Viewing
5:30 Dinner Short Course Registration*
SC1: Bioinformatics for Immuno-Oncology and Translational Research
SC2: Microbiome in Immuno-Oncology
*Separate registration required, please click here for more information.
WEDNESDAY, AUGUST 30
7:00 am Registration
7:25 Breakout Discussion Groups with Continental Breakfast
8:10 Chairperson’s Remarks
Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics
8:15 The End Game: Adjuvant γδ T Cell-Based Strategies for Consolidation and Eradication of Residual Cancer
Lawrence S. Lamb, Jr., M.N., Ph.D., Professor, Medicine; Director, Cell Therapy Laboratory, University of Alabama at Birmingham
Expanded and activated γδ T cells can significantly extend relapse-free survival (RFS) in human and animal studies of hematopoietic and solid cancers. Using glioblastoma multiforme (GBM) as a model, we show that simultaneous chemotherapy-induced upregulation of NKG2DL expression and infusion of chemotherapy-resistant gene-modified γδ T cells can result in significant RFS in a patient-derived xenograft model. We will discuss translation and early trials of these strategies in leukemia and GBM.
9:00 Personalized Adoptive Cell Therapy Using Novel XPRESIDENT® Derived Targets
Ali Mohamed, Ph.D., Vice President, CMC, Immatics US, Inc.
The lack of safe and validated targets is a major limitation for the translation of cancer immunotherapy to solid tumor indications. The XPRESIDENT® approach allows access to a novel target space using a combination of ultra-sensitive quantitative mass spectrometry, transcriptomics, immunology and bioinformatics based on the immunopeptidome of human normal and tumor tissues. We present two complementary adoptive cell therapy approaches that are based on using multiple XPRESIDENT® derived targets
9:30 Vector Manufacturing for T Cell Therapies
Klaus Kühlcke, Managing Director, EUFETS GmbH
Manufacturing technologies for high titer batches of safety-optimised retroviral vectors will be presented.
10:00 RegCAR-T™ - Development of Regulatable CAR-T Therapy
Tianjiao Wang, Ph.D., Scientist II, Research and Development, Admera Health
Chimeric Antigen Receptor (CAR) T-Cell Therapy has shown remarkable therapeutic efficacy, however, its safety is still a big concern due to severe side effects. Thus, efficacious and safe CAR-T therapy is in need of development. To regulate the efficacy and safety of CAR-T therapy, we have developed a proprietary RegCAR-T™ aptazyme technology. In RegCAR-T™, aptazymes are developed by in vitro evolution with iterative binding, partitioning and amplification. The ligands chosen are FDA-approved small molecule drugs with good safety profiles (e.g. over-the counter drugs). The ribozymes chosen function intracellularly. When a selected aptazyme is inserted into the UTR of a CAR construct, CAR expression in CAR-T cells may be controlled by a safe oral drug in a dose and/or time dependent manner. Thus, CAR-T activity can be controlled to minimize side effects while maintaining its optimal efficacy. In conclusion, RegCAR-T™ technology may enable the development of next generation regulatable CAR-T therapy with optimal efficacy and safety
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 PET-Imaging of Chimeric Antigen Receptor T Cells
David Huss, Ph.D., Senior Scientist, CAR T Cell Team Lead, Juno Therapeutics
11:45 Immunotherapy for Ovarian Cancer: One Cell at a Time
Wendy J. Fantl, Ph.D., Assistant Professor, Obstetrics and Gynecology, Stanford University School of Medicine
Multiple studies indicate that high grade serous ovarian cancer (HG-SOC) is an immunogenic tumor and can be recognized by the host immune system, yet only a subgroup of HG-SOC patients respond to immunotherapy. Here we will leverage the power of multi-parameter single cell mass cytometry to simultaneously characterize the tumor and immune cell compartments of HG-SOC tumors to discover new mechanistic biomarkers predictive of response and resistance to immunotherapy.
12:15 pm Engineering the Future of Cellular Therapy: Current Perspectives and Future Directions
Matthew Frigault, M.D., Post-Doctoral Fellow, Cellular Immunotherapy, Dana-Farber Cancer Institute
The last few years have been an exciting time for cellular therapy. CAR-T cells have offered hope for many otherwise treatment refractory patients. With the recent filing for the first FDA-approved CAR-T cell it appears that CAR-T cell therapy is here to stay. This talk will discuss additional advances in our understanding of CAR-T cell biology and genetic engineering that offer a promising future for this maturing technology.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
1:55 Chairperson’s Remarks
Richard Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio
2:00 Cytotherapy with Targeted Allogenic NK Cells
Laurent Boissel, Ph.D., Associate Director, Research & Development, NantKwest, Inc.
NantKwest has developed the NK cell line NK-92 into an “off-the-shelf” activated NK (aNK) cell therapeutic. The safety of aNK as well as their activity against a broad range of cancers have been confirmed in Phase I trials in the U.S., Canada and Europe. aNK cells can be administered in the outpatient setting and serve as a universal cell-based therapy without need for individualized patient matching. aNK cells have been bioengineered to incorporate a high antibody binding Fc-receptor (haNK). Both aNK and haNK cells can be equipped with chimeric antigen receptors (CARs) (called taNK) to further optimize targeting and potency in the therapeutic setting.
2:30 IMPACT Fusion Proteins Redirect CAR19 T Cell Cytotoxicity to Diverse Tumor Antigens
Paul Rennert, Ph.D., President and CSO, Aleta Biotherapeutics Inc.
We present a strategy to leverage sustained CD19 presentation by normal B cells to promote CAR19 T cell expansion and persistence while also redirecting their cytotoxic activity to other (non-CD19) targets via secreted fusion proteins. The technology, called IMPACT (Integrated Modules Optimize Adoptive Cell Therapy) is modular in design and can be applied to diverse antigens and tumor types. The strength of the technology is demonstrated using Her2+, BCMA+ and ROR1+ tumors.
3:00 Advancement from Boutique to Global in the 20th Year of Chimeric Antigen Receptor T Cell Trials
Bruce Levine, Ph.D., Barbara and Edward Netter Professor, Cancer Gene Therapy, University of Pennsylvania Perelman School of Medicine
Since the 1990’s, we have conducted clinical trials of gene modified T cells. Chimeric antigen receptors (CAR’s) can redirect T cells to target CD19 on B cells leukemias and lymphomas. CAR T cells have demonstrated robust and durable clinical responses in relapsed and refractory malignancies. CAR T cell design includes elements of the receptor design, gene delivery to T cells, as well as the sourcing, manufacture, testing, delivery, and administration of the final CAR T Cell Product followed by clinical management of the patient. Each of these elements provides unique challenges in an autologous drug, where the size of the lot is 1. This technology is now in global multi-center clinical trials. CAR T cells targeting new targets in hematologic malignancies and in solid tumors are underway and provide demonstration that it is possible to design immunity at will for therapeutic application.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 CD1d-Restricted NKT Cells as a Platform for Off-the-Shelf Cancer Immunotherapy
Leonid S. Metelitsa, M.D., Ph.D., Professor, Pediatrics and Immunology, Texas Children’s Cancer Center, Center for Cell & Gene Therapy, Baylor College of Medicine
The immunosuppressive tumor microenvironment (TME) impairs T-cell localization and persistence, posing a critical challenge to the development of adoptive cancer immunotherapy. My presentation will elucidate a new class of cellular immunotherapy that exploits unique natural and engineered TME-targeting properties of CD1d-restricted NKT cells. Because CD1d is monomorphic and allogeneic NKTs do not induce graft-versus-host disease, banked NKTs engineered to express chimeric antigen receptors can be used for “off-the-shelf” cancer immunotherapy.
4:45 TALEN Gene Editing for “Off-the-Shelf” Allogeneic CAR T Cell Products
Julianne Smith, Ph.D., Vice President, Translational Sciences, Cellectis
Cellectis developed a platform for generating chimeric antigen receptor (CAR)-redirected T cells from third-party healthy donors TALEN® gene editing technology. Nuclease mediated inactivation of TCR alpha abrogates the potential for T cells bearing alloreactive TCRs to mediate Graft versus Host Disease (GvHD). Additional gene inactivation events can be incorporated, permitting resistance to lymphodepleting or chemotherapeutic agents, tumor inhibition or suppression of cross T cell reactions. Such allogeneic “off-the-shelf” CAR T cell products will permit a wider application of CAR technology and lead to a new paradigm in cancer treatment.
5:15 Close of Adoptive T Cell Therapy