CAR


It is a critical moment for adoptive cell therapies. Clinical progress has been made with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), and Tumor Infiltrating Lymphocytes (TIL), making these therapies the frontrunner for curing immune-based diseases. Still, many challenges remain. The Third Annual Adoptive T Cell Therapy event will bring together immunotherapy veterans and visionaries to not just address those challenges, but to provide solutions and showcase emerging opportunities. This year’s event will address topics such as developing adoptive cell therapies for solid tumors as well as new targets of interest. Emphasis will be placed on clinical case studies to further the understanding of T cell receptors and their biology. Overall, this event will uncover the critical components needed to make adoptive T cell therapies viable.

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WEDNESDAY, APRIL 27

7:00 am Registration and Morning Coffee


NEW UNDERSTANDINGS OF T CELL BIOLOGY

8:00 Chairperson’s Remarks

Jeff Till, Ph.D., Director, External Innovation, EMD Serono R&D Institute

8:10 Jedi T Cells Provide a Universal Platform for Interrogating T Cell Interactions with Virtually Any Cell Population

Brian_BrownBrian D. Brown, Ph.D., Associate Professor, Genetics and Genomic Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai

We recently generated the first GFP-specific T-cell mouse, called the Jedi (Agudo et al. Nat Biotech 2015). The Jedi technology is the first to facilitate direct visualization of a T-cell antigen, which enables unparalleled detection of antigen-expressing cells, and make it possible to utilize the 100s of cell type-specific GFP-expressing mice, tumors, and pathogens, to gain new insight into T-cell interactions with virtually any cell population in normal and diseased tissues.

8:40 The State-of-the-Art with T cell Receptor-Based Cancer Immunotherapies

Andy_SewellAndrew K. Sewell, Ph.D., Distinguished Research Professor, Wellcome Trust Senior Investigator; Research Director, Institute of Infection and Immunity, Henry Wellcome Building, Cardiff University School of Medicine

The ab TCR enables cytotoxic T cells to scan the cellular proteome for anomalies from the cell surface. Tumor-specific TCRs can access a far greater range of targets than are available for antibodies. Engineered TCRs can be used in gene therapy and soluble molecule approaches. Next generation strategies allow circumvention of HLA-restriction. I will discuss future directions in the use of engineered T cells and TCRs in cancer immunotherapy.

DEVELOPING CELL THERAPIES AGAINST SOLID TUMORS

9:10 Tumor Infiltrating Lymphocytes for Metastatic Cutaneous and Non-Cutaneous Melanoma: A UK Perspective

John_BridgemanJohn S. Bridgeman, Ph.D., Director, Cell Therapy Research, Cellular Therapeutics Ltd.

We have established the UK’s only GMP-compliant and MHRA (Medicines and Healthcare Products Regulatory Agency) licensed unit capable of producing multiple T cell product types (CAR or TCR-modified and natural T cells (TIL)) using ‘clean room free technology’. This unit has produced melanoma-derived TIL products which have been successfully returned to patients. This study supports the success of melanoma TIL therapy seen in other centers worldwide and suggests that this is a viable means of treating a disease which has few effective options.

9:40 Design of a Highly Efficacious, Mesothelin-Targeting CAR for Treatment of Solid Tumors

Boris_EngelsBoris Engels, Ph.D., Investigator, Exploratory Immuno-Oncology, Novartis Institutes for Biomedical Research

The treatment of solid tumors with CAR T cells has shown to be challenging. We describe the design of a fully human CAR targeting mesothelin, a tumor associated antigen overexpressed in mesothelioma, pancreatic and ovarian cancer. The screen of a scFv pool has identified two scFvs, which show enhanced efficacy as CARs, superior to what is currently being used by several groups. We have performed in-depth characterization of the scFvs and CARs to gain insight into structure-activity relationships, which may influence CAR design and efficacy.

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


CAR, TCR, and TIL

10:55 ACTR (Antibody Coupled T Cell Receptor): A Universal Approach to T cell Therapy

Seth_EttenbergSeth Ettenberg, Ph.D., CSO, Unum Therapeutics

Fusing the ectodomain of CD16 to the co-stimulatory and signaling domains of 41BB and CD3z generates an Antibody Coupled T cell Receptor (ACTR). T cells expressing this receptor show powerful anti-tumor cytotoxicity when co-administered with an appropriate tumor-targeting antibody. Such cells have potential utility as a therapy to treat a wide range of cancer indications. We will describe efforts specifically targeting B-cell malignancies using a combination of ACTR T cells with rituximab.

11:25 Strategies to Optimize Tumor Infiltrating Lymphocytes (TIL) for Adoptive Cell Therapy

Shari_Pilon-ThomasShari Pilon-Thomas, Ph.D., Assistant Professor, Department of Immunology, Moffitt Cancer Center

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has emerged as a powerful immunotherapy for cancer. TIL preparation involves surgical resection of tumors and in vitro expansion of TIL from tumor fragments. ACT depends upon the presence of TIL in tumors, successful expansion of TIL, and effective activation and persistence of T cells after infusion. In this presentation, I will discuss optimization of TIL infiltration into tumors and TIL expansion for ACT in melanoma and other cancers.

11:55 Engineered T Cell Receptors for Adoptive T Cell Therapy in Solid Tumors

Jo_BrewerJo Brewer, Ph.D., Director, Cell Research, Adaptimmune Ltd.

NY-ESO-1 is a cancer antigen that is expressed by a wide array of solid and hematological tumors. An enhanced affinity TCR that recognizes this antigen is currently in Phase I/II trials for synovial sarcoma, multiple myeloma, melanoma, ovarian and esophageal cancers. Early clinical data demonstrate encouraging responses and a promising benefit/risk profile.

12:25 pm Cell Based Engineering of TCRs and CARs Using in vitro V(D)J Recombination

Gallo_MichaelMichael Gallo, President, Research, Innovative Targeting Solutions

The ability to generate antibodies and TCRs specific to a MHC/peptide complex provides for new therapeutic opportunities. A novel approach using in vitro V(D)J recombination has been shown to be a robust strategy for targeting these ultra-rare epitopes by generating large de novo repertoires of fully human antibodies, CARs, or T-cell receptors on the surface of mammalian cells. The presentation highlights the advantages of cell based engineering for the generation of cell based adoptive therapies.

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:55 Session Break


ARTIFICAL ANTIGEN PRESENTING CELLS

2:10 Chairperson’s Remarks

Jonathan Schneck, Ph.D., M.D., Professor, Pathology, Medicine and Oncology, Johns Hopkins

2:15 Artificial APCs: Enabling Adoptive T Cell Therapies

Marcela_MausMarcela V. Maus, M.D., Ph.D., Director, Cellular Immunotherapy, Mass General Hospital Cancer Center

Adoptive T cell therapies require ex vivo T cell culture systems, which can include artificial antigen presenting cells. We will review several types of natural and artificial APCs and how they can be optimized to generate strong memory and effector T cells usable for adoptive transfer.

2:45 Immunoengineering of Artificial Antigen Presenting Cells, aAPC: From Basic Principles to Translation

Jonathan_SchneckJonathan Schneck, Ph.D., M.D., Professor, Pathology, Medicine and Oncology, Johns Hopkins

Artificial antigen presenting cells (aAPCs) are immuno-engineered platforms which advance adoptive immunotherapy by reducing the cost and complexity of generating tumor-specific T cells. Our new approach, termed Enrichment and Expansion (E+E), utilizes paramagnetic nanoparticle-based aAPCs to rapidly expand both shared tumor antigen- and neoepitope-specific CTL. Streamlining the rapid generation of large numbers of T cells in a cost-effective fashion can be a powerful tool for immunotherapy.

3:15 Vector Free Engineering of Immune Cells for Enhanced Antigen Presentation

Armon Sharei, Ph.D., CEO, SQZ Biotech

In this work we describe the use of the vector-free technology to deliver antigen protein directly to the cytoplasm of antigen presenting cells to drive a powerful antigen specific T-cell response. Current efforts to use antigen presenting cells to drive T-cell responses rely on an inefficient process called cross-presentation that relies on material escaping the endosome and entering the cytoplasm. We believe that by delivering antigen directly to the cytoplasm of antigen presenting cells we can overcome this long standing barrier and drive powerful and specific T-cell responses. Our results show that by adoptively transferring antigen presenting cells that have antigen delivered into them we can drive a significant T-cell response. Specifically, we found that this results in a ~50x increase in antigen specific T-cells in vivo when compared to endocytosis. This advance has the potential to dramatically enhance the therapeutic potential of therapeutic vaccination with antigenic material for the treatment of a wide variety of cancers. Indeed, the ability to deliver structurally diverse materials to difficult-to-transfect primary cells indicate that this method could potentially enable many novel clinical applications.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem-Solving Breakout Discussions

Moving Adoptive T Cell Therapies Toward the End Game

Moderator: Richard S. Kornbluth, M.D., Ph.D., President & CSO, Multimeric Biotherapeutics, Inc.

 

  • Antigenic targets for CAR-T cells: Are we limited to antibody-accessible surface antigens?
  • Mutanome-specific T cells: how robust are the technologies for making them?
  • Tumor-infiltrating lymphocytes (TILs) and TCR-transgenic T cells: How are they affected by the tumor microenvironment (TME) and limitations on MHC presentation by tumor cells?
  • Scalability of personalized autologous T cell therapy vs. off-the-shelf allogeneic approaches: which manufacturing process will end up winning in the end?
  • Toxicity avoidance: methods for turning off rogue T cells vs. using short-term gene expression with mRNA

 

Focusing CAR, TCR, and TIL for Effective Therapies

Moderator: John S. Bridgeman, Ph.D., Director, Cell Therapy Research, Cellular Therapeutics Ltd.

 

  • What needs to be addressed to increase the potential for CAR-T in solid cancers?
  • Are TCR engineered T-cells for highly mutated cancers limited by their targeting capacity?
  • Will the success of TIL in melanoma be mirrored in other cancer indications?
  • Where should CAR-T, TCR and TIL ACT be focused and how will the three strategies work together in the future?

 

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

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THURSDAY, APRIL 28

8:00 am Morning Coffee

8:30 Chairperson’s Remarks

Richard S. Kornbluth, M.D., Ph.D., President & CSO, Multimeric Biotherapeutics, Inc.

8:35 CD40 Ligand (CD40L) and 4-1BB Ligand (4-1BBL) as Keys to Anti-Tumor Immunity

Richard_KornbluthRichard S. Kornbluth, M.D., Ph.D., President & CSO, Multimeric Biotherapeutics, Inc.

CD40 ligand (CD40L) and 4-1BB ligand (also called CD137L) activate immunity by binding to and clustering their receptors. We have solved the receptor clustering problem by creating fusion proteins that contain many TNFSF trimers. In this talk, we will discuss how soluble multi-trimer forms of TNFSFs such as CD40L and 4-1BBL have many important applications in cancer immunotherapy.

9:05 Portable Genetic Adjuvants Inspired by the EBV Latent Membrane Protein-1 (LMP1)

Richard S. Kornbluth, M.D., Ph.D., President & CSO, Receptome, LLC

The strongest CD8+ T cell response in humans occurs in Epstein-Barr Virus (EBV) infection and is due to LMP1, a CD40 receptor homologue. The LMP1 nucleic acid sequence activates dendritic cells and adjuvants RNA, DNA, and viral vaccines. Joining the LMP1 N-terminal domain with IPS-1 forms LMP1-IPS-1, a STING pathway activator and vaccine adjuvant. This technology provides a new approach for using CD40 and the STING pathway for cancer immunotherapy.

Harnessing NK Cells

9:35 Overview of NK Cell and T Cell Therapies For Hematologic Malignancies After Hematopoietic Stem Cell Transplantation
Conrad (Russell) Y. Cruz M.D., Ph.D., Assistant Professor of Pediatrics; Director, Translational Research Laboratory, Program for Cell Enhancement and Technologies for Immunotherapy (CETI), Children's National

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

GENE MODIFICATION STRATEGIES

11:05 Genetic Modification of CAR-T cells for Solid Tumors: Challenges and Advancement

Pranay Khare, Ph.D., Independent Consultant

CAR-T cell engineering for adoptive T cell therapy have consistently shown exciting results by several groups in hematologic malignancies. But, limited success has been achieved in solid tumor field with CAR-T cell therapy. Efforts have been focused to improve CAR-T cells specificity, potency and persistence with variety of non-viral and viral vectors. This talk will focus on different strategies and lessons learned from hematologic malignancies and other novel ways to overcome the obstacles in solid tumor field.

11:35 Engineering Human T Cell Circuitry 

Alex_MarsonAlex Marson, Ph.D., UCSF Sandler Fellow, University California, San Francisco

T cell genome engineering holds great promise for cancer immunotherapies and for cell-based treatments for immune deficiencies, autoimmune diseases and HIV. We have overcome the poor efficiency of CRISPR/Cas9 genome engineering in primary human T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs can promote targeted genome sequence replacement in primary T cells by homology-directed repair (HDR), which was previously unattainable with CRISPR/Cas9. This provides technology for diverse experimental and therapeutic applications.

12:05 pm Engineering the Genome of CAR T Cells: From Therapeutic Procedures to Products

Andre_ChoulikaAndré Choulika, Ph.D., CEO and Chairman, Cellectis

Cellectis’ therapeutics programs are focused on developing products using TALEN®-based gene editing platform to develop genetically modified T cells that express a Chimeric Antigen Receptors (CAR) for cancer treatment. The first product, UCART19, T cells has been gene-edited to suppress GvHD and enable resistance to an Alemtuzumab treatment. The objective of this first product is to convert the CART cell therapy for an autologous approach to an off-the-shelve allogeneic CART product that can be produced in a cost effective fashion, stored, shipped anywhere in the world and immediately available to patient with an immediate unmet medical need.

12:35 End of Adoptive T Cell Therapy

5:15 Registration for Dinner Short Courses


Recommended Dinner Short Course*

SC11: Clinical Prospects of Cancer Immunotherapy

*Separate registration required.


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