2014 Archived Content

Adoptive T Cell Therapy

Day 1 | Day 2 | Download Brochure | Speaker Bios 

Adoptive T cell therapy has the potential to increase antitumor immunity, enhance vaccine efficacy, and limit graft-versus-host disease (GVHD). Recent advances in protein engineering and molecular biology have increased the feasibility of using genetically engineered T cells to treat disease, leading to an influx of new discoveries and techniques. Cambridge Healthtech Institute's Inaugural  Adoptive T Cell Therapy will review the latest strategies for target discovery, vector selection, and chimeric antigen receptors (CAR) against tumor antigens. Experts will discuss techniques for increasing specificity, choosing domains, and incorporating fusion proteins into T cells. Dosing uncertainties such as toxicity threshold and antigen detection will also be addressed.  Overall, this inaugural event will focus on issues facing the field with an emphasis on engineered T cells and the use of adoptive t cell transfer to facilitate therapeutic treatments for cancer, infectious diseases, and bone marrow transplants.


WEDNESDAY, MAY 7


RECOMMENDED PRE-CONFERENCE SHORT COURSES*

Introduction to Adoptive T Cell Therapies - View Detailed Agenda 

*Separate registration required

7:00 am Registration and Morning Coffee


Strategies for Target Discovery, Selection & Validation 

8:00 Chairperson's Opening Remarks

Nancy L. Parenteau, Ph.D., Co-Founder, President & CSO, Ingenium BioTherapy Corporation


» 8:10 OPENING KEYNOTE PRESENTATION:

Engineered T Cell Therapies for Cancer

MarcelaMausMarcela V. Maus, M.D., Ph.D., Director, Translational Medicine and Early Clinical Development, Translational Research Program, Abramson Cancer Center, University of Pennsylvania

This presentation will provide background on T cell biology and costimulation as well as the synthetic biology of chimeric antigen receptors and how they were developed. Preclinical data and clinical data in leukemia and preclinical and early-phase translation of engineered T cells in several cancers will also be presented.

8:40 Innovative Approaches to Effective T cell Transfer Therapy of Cancer

DanielPowellDaniel J. Powell, Jr., M.D., Assistant Professor, Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

The adoptive transfer of tumor-reactive T cells has emerged as a “game changer” in the effective treatment of melanoma and leukemias, but challenges exist to its widespread application in other malignancies. This presentation focuses on improved methodologies and approaches that allow for isolation of rare tumor-reactive TILs from non-melanoma cancers, and the development of systems that better enable gene-engineered T cells to persist after infusion, that focus their cytolytic activity on cancers cells, not normal organ tissues, and that permit versatility in antigen targeting to broaden patient access to this promising new immunotherapeutic approach. These next generation strategies will be discussed and stand to improve the efficacy, safety and access to CAR T cell therapy for cancer. 

9:10 A Pipeline for Generating Affinity-Enhanced TCRs for Adoptive T Cell Therapy

EllenBorderEllen Border, D.Phil., Senior Scientist, Protein Engineering, Adaptimmune Ltd.

This presentation outlines the processes comprising Adaptimmune’s TCR pipeline, beginning with target antigen selection and validation. TCRs directed towards these antigens are isolated and characterized, using a range of assays, and a subset is selected for affinity optimization. Panels of affinity enhanced mutants are then tested for efficacy and specificity in cells to identify lead candidates for full preclinical assessment, and progression to clinical trials.

9:40 Predictive Biomarkers in Adoptive T Cell Therapy Using Tumor-Infiltrating Lymphocytes

LaszloRadvanyiLaszlo Radvanyi, Ph.D., Professor, Melanoma Medical Oncology, University of Texas , MD Anderson Cancer Center

This talk will present work on a comprehensive project identifying predictive biomarkers in TIL-treated patients both on the infused T cells, as well as biomarkers in tumor microenvironment of tumors from TIL treated patients. We have identified a number of candidate biomarkers that can be validated in further trials and also shed light on the mechanism of action of TIL and how tumor microenvironment factors regulate T-cell infiltration and TIL response.

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


Strategies for T Cell Engineering 

11:10 Engineering Genetic Resistance to HIV in T Cells

MattPorteusMatthew Porteus, M.D., Ph.D., Associate Professor, Pediatrics (Cancer Biology), Stanford School of Medicine

We have used the tools of genome editing to demonstrate the feasibility and power of genetically "stacking" multiple anti-HIV genes in creating cells that are resistant to both CCR5-tropic and CXCR4-tropic HIV. This presentation will discuss that work and the future directions we are exploring to translate the concept into therapy for patients with HIV.

11:40 Enhancing the IQ of CAR T Cells

MichaelJensenMichael C. Jensen, M.D., Professor, Pediatrics, University of Washington School of Medicine; Director, Ben Towne Center for Childhood Cancer Research/Seattle Children's Research Institute; Joint Member, Program in Immunology, Fred Hutchinson Cancer Research Center

Targeted eradication of cancer by adoptive transfer of antigen specific T cells is the subject of intensive clinical exploration. While many of the key conceptual and technical barriers that have previously limited translation to human clinical trials have been overcome, as reflected by the growing number of FDA IND-supported studies in progress, significant refinement is needed to evolve this therapeutic modality for reproducibly effective and safe applications in the oncology clinic. This talk will focus on technologies in development that utilize principles of synthetic biology and bioengineering to equip CAR T cells with regulated functional outputs.

12:10 pm Enjoy Lunch on Your Own

1:40 Session Break 


Chimeric Antigen Receptor Design 

2:00 Chairperson's Remarks

Michael C. Jensen, M.D., Professor, Pediatrics, University of Washington School of Medicine; Director, Ben Towne Center for Childhood Cancer Research/Seattle Children's Research Institute; Joint Member, Program in Immunology, Fred Hutchinson Cancer Research Center

2:05 The Principles of Chimeric Antigen Receptor Design

MichelSadelainMichel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering & Gene Transfer and Gene Expression Laboratory; Stephen and Barbara Friedman Chair, Memorial Sloan-Kettering Cancer Center

A multitude of CARs have been reported over the past decade, targeting an array of cell surface tumor antigens. Their biologic functions have dramatically changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. These have recently shown clinical benefit in patients treated with CD19-targeted autologous T cells and represent a new class of drugs with exciting potential for cancer immunotherapy.

2:35 ErbB-Targeted CAR T Cell Immunotherapy of Cancer: A Strategy to Maximize the Window of Therapeutic Opportunity

JohnMaherJohn Maher, Consultant and Senior Lecturer in Immunology, Department of Research Oncology, King's College London

We have developed a CAR named T1E28z that targets the extended ErbB network. Engineered T cells are expanded and enriched using a co-expressed IL-4-responsive chimeric cytokine receptor. Efficacy of the resultant "T4 immunotherapy" has been demonstrated in several tumor models in vivo, without significant accompanying toxicity. To de-risk this approach in man, phase 1 testing will be performed in patients with head & neck cancer.


NEW Techniques in T Cell Therapy 

3:05 Dynamic Intravital Tracking of Immune Cell Migration and Interaction with Single Cell Resolution

Alex Y. Huang, M.D., Ph.D., Associate Professor, Pediatrics, Pathology & Biomedical Engineering; Director, Pediatric Hematology-Oncology Fellowship Program, Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine

To improve efficacy and to understand the biology of how adoptive T cell therapy works in vivo, attention must be paid to how immune cells behave and interact within host tissue and tumor microenvironment. The application of intravital two-photon microscopy in preclinical animal models allows the visualization and tracking of these intricate mutli-cellular processes in 3-dimensions over time. In turn, these observations yield new insights into cellular biology that were previously under-appreciated using traditional experimental tools. These novel insights promise to provide new scientific rationale in designing next generation adoptive T cell therapy.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:20 Problem Solving Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

TABLE: Strategies for T Cell Manufacture

Moderator: Joseph C. Laning, Ph.D., Co-founder, Ingenium BioTherapy Corporation; Vice President, Research & Development, Provia Labs

  • Given the added economic and logistical challenges unique to (N of 1) immunotherapies, what areas present the greatest challenges? What are the top three manufacturing challenges face therapeutic developers and regulators?
  • In order to work effectively with regulators and continue moving advanced cellular therapies to the clinic what development, manufacturing, and testing elements look to be priorities?
  • The promise to provide active and targeted therapies for intractable diseases is possible, how do we balance aggressive development and assurance of safety to avoid setbacks?
  • What resources, technology, or infrastructure would be most helpful in advancing cellular immunotherapeutics?

TABLE: Preclinical Evaluation of Enhanced Affinity T Cell Receptors for Adoptive T Cell Therapy

Moderator: Joanna E. Brewer, Ph.D., Group Leader, Cellular Biology, Adaptimmune Ltd.

  • Fine-tuning TCRs by engineering, to give viral-like affinities, and transducing into T cells
  • Consequences of bypassing thymic selection
  • Maintaining TCR target specificity
  • Assessing the potential for off-target toxicity against normal tissues

TABLE: Microenvironmental Dynamics Affecting Adoptive Cellular Therapy in vivo 

Moderator: Alex Y. Huang, M.D., Ph.D., Associate Professor, Pediatrics, Pathology & Biomedical Engineering; Director, Pediatric Hematology-Oncology Fellowship Program, Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine

  • Regulation of the host microenvironment
  • Technologies for visualization and tracking of multi-cellular processes
  • New scientific rationale in designing next generation adoptive T cell therapy

5:20 Networking Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day


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