Emerging Techniques in Synthetic Biology

Cambridge Healthtech Institute’s Inaugural

Emerging Techniques in Synthetic Biology

Customizing Immune Cells for More Effective Immunotherapies
August 31 - September 1, 2017 | Sheraton Boston | Boston, MA


Cell-based immunotherapies provide a unique opportunity to incorporate synthetic biology approaches to create safer, more effective cancer therapies. However, despite numerous advances, the field has not reached the point where genetic parts can be predictably combined to achieve a desired outcome. At Cambridge Healthtech Institute’s Inaugural Techniques in Synthetic Biology event, industry visionaries will review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. Cellular engineering and genome editing of host cells to improve the efficacy of cell-based cancer therapeutics will also be addressed. Overall, this event will build a solid foundation for a robust and impactful synthetic biology toolbox.



Final Agenda

THURSDAY, August 31

7:45 am Registration & Morning Coffee

NEW TECHNIQUES IN T CELL ENGINEERING

8:25 Chairperson’s Opening Remarks

Wilson Wong, Ph.D., Assistant Professor, Biomedical Engineering, Boston University


8:30 KEYNOTE PRESENTATION: Reining in T Cell Therapies in 2 Dimensions Should Promote Both Safety and Efficacy

David M. Spencer, Ph.D., CSO, Research & Development, Bellicum Therapeutics

Despite great promise, adoptive cell therapies for solid tumors are still limited by efficacy and safety challenges. Using chemically induced dimerization (CID) that taps into fundamental properties of cell biology, we have developed orthogonal switches that permit regulation of T cell activity and persistence alongside survival control. Independent regulation of co-stimulation and apoptosis in the same cell is now possible using a scalable, clinically compatible process.

9:00 Synthetic Biology in Cellular Immunotherapy

Wilson Wong, Ph.D., Assistant Professor, Biomedical Engineering, Boston University

The transfer of tumor-targeting T cells to patients is a promising approach for cancer immunotherapy. Despite these encouraging results, many challenges remain to be addressed before T cell therapy can be widely adopted. Here I will describe our efforts in using synthetic biology to develop genetic circuits and switches for modulating T cell activation. These genetic tools will provide tools for managing the toxicity associated with T cell therapy.

9:30 Engineering Smarter and Stronger T Cells for Cancer Immunotherapy

Yvonne Y. Chen, Ph.D., Assistant Professor, Chemical and Biomolecular Engineering, University of California Los Angeles

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown curative potential against advanced B-cell malignancies, but a number of challenges remain to be addressed before adoptive T-cell therapy can achieve broad application. Here, we discuss two examples in which synthetic-biology principles are applied to the engineering of therapeutic T cells to overcome challenges observed in the clinic. We will first discuss the rational design and systematic optimization of bispecific, OR-gate CAR-T cells that robustly eliminate target cells expressing either CD19 or CD20, thereby reducing the risk of antigen escape in the treatment of B-cell malignancies. We will also present novel CARs that effectively rewire T-cell responses to transforming growth factor beta (TGF-b), converting this potent immunosuppressive cytokine into a T-cell stimulant and increasing the efficacy of adoptive T-cell therapy against solid tumors. These results highlight the potential of synthetic biology in generating novel mammalian cell systems with multifunctional outputs for therapeutic applications.

10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing)

10:45 PANEL DISCUSSION: Synthetic Biology Approaches to Immuno-Oncology

Moderator: Wilson Wong, Ph.D., Assistant Professor, Biomedical Engineering, Boston University

  • Gating strategies
  • Antigen presentation
  • Activation and kill switches for safer therapies
  • Innovative approaches to activation and engagement

Panelists: Yvonne Y. Chen, Ph.D., Assistant Professor, Chemical and Biomolecular Engineering, University of California Los Angeles

David M. Spencer, Ph.D., CSO, Research & Development, Bellicum Therapeutics

Justin Eyquem, Ph.D., Research Fellow, Immunology, Memorial Sloan Kettering Cancer Center

Alex Marson, M.D., Ph.D., Assistant Professor, Microbiology and Immunology, Divisions of Infectious Diseases and Rheumatology, Department of Medicine, UCSF Diabetes Center, University of California San Francisco

GENOME EDITING

11:45 Genome Modification and Evolution of Cells

Farren Isaacs, Ph.D., Assistant Professor, Molecular Cellular & Developmental Biology, Systems Biology Institute, Yale University

12:15 pm Sponsored Presentation (Opportunity Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

GENOME EDITING (CONT.)

2:25 Chairperson’s Remarks

David M. Spencer, Ph.D., CSO, Research & Development, Bellicum Therapeutics

2:30 Precision T Cell Engineering to Advance CAR Therapy

Justin Eyquem, Ph.D., Research Fellow, Immunology, Memorial Sloan Kettering Cancer Center

Transducing T cells with synthetic chimeric antigen receptors (CARs) is a promising approach for treating certain types of cancer. We are developing innovative strategies to study CAR immunobiology and improve the performance and the safety of CAR T cells. We are using genome editing to target CAR genes to specific loci for precise expression control and augmented tumor killing activity.

3:00 Decoding T Cell Circuitry

Alex Marson, M.D., Ph.D., Assistant Professor, Microbiology and Immunology, Divisions of Infectious Diseases and Rheumatology, Department of Medicine, UCSF Diabetes Center, University of California San Francisco

Functional testing of human genome sequences in primary immune cells has been largely impossible until recently. We developed a CRISPR-Cas9 platform that enables knock-out and knock-in genome-editing in human T cells by electroporation of Cas9 ribonucleoproteins (Cas9 RNPs). Cas9 RNP technology holds great potential for therapeutic genome engineering. We aim to understand how sequence variation throughout the human genome affects T cell circuits in health and disease.

3:30 Highly Efficient, ZFN Driven, Derivation of Universal T Cells

Gary Lee, Ph.D., Director, Genome Editing, Sangamo Therapeutics

Genome (CCR5) edited T cells have been extensively evaluated in patients with HIV and were well tolerated. For applications in immune-oncology, we have developed ZFN reagents that can efficiently derive universal (TCR and HLA class I KO) T cells (>90% double KO without selection). In addition, >85% targeted gene addition was achieved with locus specific donor molecules that encode various gene expression cassettes (e.g. GFP, CAR or TCR).

4:00 Refreshment Break

4:30 Sponsored Presentation (Opportunity Available)

5:00 PANEL DISCUSSION Beyond Immuno-Oncology: Where is Synthetic Biology Headed?

Moderator to be Announced

  • Synthetic biology vs. other engineering fields
  • Computational and experimental approaches to engineering cell behavior
  • Additional indications for synthetic biology application

Panelists: Tara L. Deans, Ph.D., Assistant Professor, Bioengineering, University of Utah

Kole T. Roybal, Ph.D., Assistant Professor, Microbiology, Immunology, University of California San Francisco

Ron Weiss, Ph.D., Professor, Biological Engineering, Synthetic Biology Center, Massachusetts Institute of Technology

Shigeki Miyake-Stoner, Ph.D., Translational Specialist, Molecular and Cell Biology Laboratories, Salk Institute for Biological Studies

6:00 End of Day

6:00 Dinner Short Course Registration*

SC3: Study Design and Statistical Data Analysis of Flow Cytometry Assays for Cancer Immunotherapy

SC4: CRISPR/Cas9 Applications in Immunotherapy

*Separate registration required, please click here for more information.

FRIDAY, SEPTEMBER 1

8:00 am Registration and Morning Coffee

ENABLING TECHNOLOGIES FOR FUTURE DIRECTIONS

8:25 Chairperson’s Opening Remarks

Tara L. Deans, Ph.D., Assistant Professor, Bioengineering, University of Utah

8:30 Hacking Immune Cells with Synthetic Notch Receptors to Expand Their Therapeutic Potential

Kole T. Roybal, Ph.D., Assistant Professor, Microbiology, Immunology, University of California San Francisco

Immune cell therapies for cancer could benefit from more sophisticated engineering that 1) allows the cells to better discriminate diseased tissue from normal tissue and 2) expands their capabilities to overcome inhospitable tumor microenvironments. Synthetic Notch receptors are a versatile platform to address these problems allowing for customization of the therapeutic response programs of immune cells and the enhancement of their ability to discriminate diseased from healthy tissue.

9:00 Phospho Neoantigens: Approaches to Neoantigen Prediction

Mark Cobbold, MRCP, Ph.D., Associate Professor, Massachusetts General Hospital Cancer Center

9:30 Mammalian Synthetic Biology: From Parts to Modules to Therapeutic Systems

Ron Weiss, Ph.D., Professor, Biological Engineering, Synthetic Biology Center, Massachusetts Institute of Technology

Synthetic biology is revolutionizing how we conceptualize and approach the engineering of biological systems. Recent advances in the field are allowing us to expand beyond the construction and analysis of small gene networks towards the implementation of complex multicellular systems with a variety of applications. In this talk I will describe our integrated computational / experimental approach to engineering complex behavior in a variety of cells, with a focus on mammalian cells. In our research, we appropriate design principles from electrical engineering and other established fields. These principles include abstraction, standardization, modularity, and computer aided design. But we also spend considerable effort towards understanding what makes synthetic biology different from all other existing engineering disciplines and discovering new design and construction rules that are effective for this unique discipline.

10:00 Coffee Break

10:30 Synthetic Biology Approaches for Engineering Platelets as Delivery Systems for Treating Disease

Tara L. Deans, Ph.D., Assistant Professor, Bioengineering, University of Utah

We are currently using approaches in synthetic biology to direct hematopoietic stem cell differentiation to mass-produce platelets and red blood cells in vitro, in addition to enabling them to function as targeting and carrier devices for the delivery of biomolecules to areas of the body requiring intervention. I will demonstrate how tools in synthetic biology can be used to control genes and pathways that result in changes in stem cell fate decisions, in addition to reprogramming platelets to function as novel therapeutic diagnostic and delivery vehicles.

11:00 A Modular Approach to Engineering a Tumor-Specific Oncolytic Adenovirus with Small Molecule-Controlled Expanded Tropism

Shigeki Miyake-Stoner, Ph.D., Translational Specialist, Molecular and Cell Biology Laboratories, Salk Institute for Biological Studies

There are diverse and promising applications for viral vectors as vaccines, gene therapies, and oncolytic therapies, but they can only be realized if we can precisely engineer modifications to viruses to give them new desired properties. We have designed a strategy for assembling adenovirus genomes from a growing library of modules that are easy to genetically manipulate. Using our platform, we have designed an oncolytic adenovirus with selective tumor replication without the loss of replication potency, and that can be pharmacologically induced to infect cells via an additional receptor on refractory metastatic tumors in vivo.

11:30 Close of Emerging Techniques in Synthetic Biology



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