Plenary Session Spotlight

Thursday May 4 09:00 – 10:30

Catherine Bollard, MBChB, MD
Director, Program for Cell Enhancement and Technologies for Immunotherapy (CETI), Children’s National Medical Center
Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine, The George Washington University
United States
Session Chair
ISCT President 2016-2018

The rapidly advancing field of T cell immunotherapy is a major treatment innovation with the potential to deliver safer, more effective treatments than are currently available, for cancer as well as for life-threatening infections. One approach has been to expand antigen specific T cells as described by Helen Heslop in her overview of the virus specific T cell field, to retarget T cells to attack malignant cells by the insertion of artificial T cell receptors and gene editing strategies as presented by Chiara Bonini and strategies to direct and arm T cells by insertion of a chimeric antigen receptor (CAR) as discussed by Martin Pule. We hope that the audience will find in this Presidential Plenary session a broad overview of the most clinically promising cell therapies in this fast moving field.

Engineered T-cell Therapy, Smarter Targets and Smarter Targeting

  Martin Pule, MB BCh
Director of CAR Program & Senior Lecturer, University College London
Founder and Chief Scientific Officer, Autolus Ltd.
United Kingdom

Chimeric antigen receptor therapy faces several challenges when moving from targeting CD19. Target antigens which are completely specific for the tumour are rare and many targets risk targeting tissues which are not as dispensable as the B-cell compartment. Targeting single antigens risks tumour escape. I will discuss some approaches that can be used to overcome these problems. Careful targeting of very particular antigens can reduce targeting of normal tissues to tolerable levels. I will also discuss alternative synthetic biology approaches which link receptors together can target patterns of antigen expression.

Virus Specific T Cells to Prevent and Treat Viral Infections After HSCT

  Helen Heslop, MD
Dan L Duncan Chair, Professor of Medicine and Pediatrics
Center for Cell and Gene Therapy,
Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital
United States

Viral infections are still a major complication during the period of immune suppression that follows allogeneic hematopoietic stem cell transplantation (HSCT). Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Multiple studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported encouraging response rates. Current efforts are investigating broadening the applicability of this approach by simplifying manufacture and optimizing “off the shelf” approaches.

TCR Gene Editing of Memory Stem T Cells for Cancer Treatment

Chiara Bonini, MD
Head of the Experimental Hematology Unit
San Raffaele Scientific Institute

Adoptive T cell therapy relies on the ability of T lymphocytes to recognize and destroy specific targets, on microbes or tumors, through their T cell receptors (TCR), leading to efficient killing and long-term protection against diseases. To be effective against cancer, T cells needs to be 1. Specific for cancer antigens, 2. Able to expand and persist long enough to mediate a long lasting clinical response, 3. Able to counteract the immunosuppressive tumor microenvironment.

TCR genetic engineering represents a suitable approach to generate large numbers of tumor specific T cells. The core of this approach is the transfer in patients’ T cells of genes encoding for rare tumor-specific TCR. However, the simple transfer of tumor specific TCR genes into T cells is affected by some limitations: genetically modified T cells shall express four different TCR chains, that might mispair, leading to unpredictable toxicity and to an overall dilution of the tumor specific TCR on lymphocyte surface, thus limiting the efficacy of therapeutic cellular product. To overcome these issues, we developed a TCR gene editing procedure, based on the knockout of the endogenous TCR genes by transient exposure to alfa and/or beta chain specific Zinc Finger Nucleases (ZFNs), followed by the introduction of tumor-specific TCR genes by lentiviral vectors. The TCR gene editing technology, proved safer and more effective than conventional TCR gene transfer in vitro and in animal studies, in models of acute myeloid leukemia and multiple myeloma.  We developed protocols to generate high numbers of TCR edited memory stem T cells and central memory T cells, lymphocyte subsets endowed with long term persistence capacity. The immunosuppressive environment that such innovative cellular products will encounter once infused to cancer patients represents an additional challenge that will be discussed during the presentation.

Thursday May 4 13:45 – 15:15


Giovanna Lombardi, PhD
Professor of Human Transplant Immunology
King’s College London
United Kingdom
Session Chair

The cellular mechanisms involved in regulation of the immune response In Vivo have been the subject of intense research for over 30 years. Clinically the first use of mesenchymal stromal cells to downregulate immune responses In Vivo was the seminal work by Katerina LeBlanc and colleagues in the treatment of steroid refractory GvHD and trials are ongoing with regulatory T cells (Treg) in the treatment of autoimmune disease and prevention of solid organ transplant rejection. This is another rapidly advancing field and this plenary session presents the current state of the art of cellular immunoregulation with
MSCs, Tregs and, excitingly, CAR-Tregs in autoimmune disease and solid organ transplantation. All of the speakers are focused on clinical translation and will present the developments of these therapies from basic science to clinical trial.

On Target: Chimeric Autoantibody Receptor (CAAR) T Cells for Autoimmune Disease Therapy

Aimee Payne, MD, PhD
Albert M. Kligman Associate Professor of Dermatology
University of Pennsylvania
United States

Therapy of autoimmunity relies on chronic immunosuppression, which causes significant morbidity and mortality. Ideally, therapy should target only the disease-causing autoimmune cells while sparing the cells that provide protective immunity. Recently, we developed a novel targeted cellular immunotherapy for the autoantibody-mediated disease pemphigus vulgaris (PV), based on the revolutionary chimeric antigen receptor technology that has cured previously refractory B cell cancers. By using the PV autoantigen desmoglein 3 as the extracellular domain of a chimeric autoantibody receptor (CAAR), T cells target the anti-desmoglein 3 B cell receptor, thus causing antigen-specific B cell depletion. In vivo proof-of-concept for CAAR-T cell therapy of PV, as well as other applications of chimeric immunoreceptor technology to autoimmune disease therapy will be discussed.

Next Generation Regulatory T Cell Therapy

Megan Levings, PhD
Professor, Department of Surgergy
University of British Columbia
Head, Childhood Diseases Theme
BC Children’s Hospital Research Institute

Cellular therapy with Tregs is a promising strategy to induce tolerance in a number of clinical contexts. Tregs currently used in clinical trials are typically polyclonal and unmodified. Ongoing basic-science work has provided considerable new insight into multiple facets of Treg biology, including their stability, homing, and functional specialization; integrating these basic-science discoveries with clinical efforts will support the development of next generation therapeutic Tregs with enhanced efficacy. Strategies to improve and tailor Tregs for cell therapy to induce tolerance will be discussed.

Mesenchymal Stromal Cell Therapy for Autoimmune Diseases. Facts and Future.

  Fernando Figueroa, MD, FACP
Professor of Medicine
Director, Program for Translational Research in Cell Therapy
University of Los Andes

Recent data suggests MSCs can rescue injured tissue by transferring their mitochondria to damaged target cells. We will present data indicating MSCs also transfer mitochondria to lymphoid cells, a finding in support of the notion that MSCs might exert immunoregulatory effects by modifying the metabolic state of target immunocompetent effectors.

Friday May 5 13:45-15:15


Simon Ellison, MBA
Senior Manager, Advanced Therapies
Fisher BioServices UK
United Kingdom
Session Chair

Cell and gene companies have moved through the research phase and evolved past development into viable, market ready organisations.  This has been, and continues to be, a rocky road.  However the evidence shows that success is reliant on creating a therapy that can treat patients beyond a clinical trial.

This session will draw on learning experiences from other industries and combine them with examples from the cell and gene therapy industry to highlight the criticality of maintaining a patient focus throughout therapy development.


Commercialization Requirements for Cell and Gene Therapies

Olav Hellebø, MBA
United Kingdom

How unique are we? Do Advanced Therapies require different commercialisation capabilities than traditional pharmaceuticals? How do logistics and market access requirements compare?

Barriers to delivery and adoption in healthcare systems: a clinicians perspective

Marc Turner, MBChB, PhD, MBA
Medical Director
Scottish National Blood Transfusion Service

The development of cellular therapies rests on sound academic, quality, nonclinical and clinical data leading to successful Marketing Authorisation and Health Technology Assessment. However in focussing on these challenges developers can sometimes miss key issues within the healthcare environment which can be critical in determining whether the product will be clinically adopted or not. These include (inter alia) an understanding of the supply chain(s) which extend from procurement of starting materials through to delivery of the finished product to the patient and which vary between different types of product, organisational infrastructure and precision in placement of the product within the diagnostic and clinical care pathway. When starting with the end in mind, it is the adoption of the product into routine clinical practice which is the common ultimate objective for academics, commercial developers and clinicians alike.

Barriers to successful development of cellular therapies: What can be done to overcome them?

Kurt Gunter, MD
Chief Medical Officer
Cell Medica Inc
United States

Although cellular therapies are widely recognized for their enormous potential to treat and possibly cure human disease, progress in the field has been slow, especially when progress is measured by the emergence of approved and commercially viable products.  In this presentation, taking both a historical and forward looking perspective, I will review some of the challenges faced by our field, analyze some of the major barriers to successful development and suggest potential pathways forward.  Audience participation will be encouraged!

Patient Centric Development within Big-Pharma

Sven Kili, MD
VP, Head of Gene Therapy Development
United Kingdom
  • Give an update on the commercialisation of Strimvelis
  • Overview of the path to market for a rare disease GT and some of the issues faced.
  • What a large Pharma company can add to the development of a cell and gene therapy

Saturday May 6 08:45-10:15

Professor, Sydney Medical School, University of Sydney
Session Chair

Increasingly, the cells, tissues and organs being deployed as advanced therapeutic products are being engineered prior to delivery to generate or enhance therapeutic efficacy. This session, which is designed to complement and expand upon the highly successful ‘Evolution of Species’ session at the 2016 Singapore Annual Meeting, will highlight key examples of this kind of cutting-edge biological engineering. Attendees will not only gain an understanding of what is happening in clinics right now, but will also  glimpse the future as they are led on a fascinating journey – from genes, through organelles and finally to whole organs – with talks from the leaders in the field.

Mitochondrial donation to prevent mitochondrial DNA disease

Professor Sir Doug Turnbull, MBBS, PhD, FRCP, FMedSci
Wellcome Trust Centre for Mitochondrial Research, Newcastle University
United Kingdom
Mitochondrial donation is a new IVF technique to prevent the transmission of mitochondrial DNA disease. Mitochondrial DNA is purely maternally inherited. Mitochondrial Donation involves the transfer of the nuclear DNA from an oocyte or zygote from a mother with mitochondrial DNA mutations into an enucleated oocyte or early zygote from a donor. Mitochondrial donation has undergone extensive ethical and regulatory scrutiny in the UK and the Mitochondrial Donation Regulations were passed by both Houses of Parliament. The final approval for cautious use of this technique was given in December 2016 by the Human Fertilisation and Embryology Authority and a study to look at the long term follow up of children born is due to start in April 2017.

Gene therapy in severe immunodeficiency

Prof Adrian Thrasher, PhD MB BS FBS FRCP FRCPCH FRCPath FMedSci
Professor of Paediatric Immunology
Programme Lead, Infection, Immunity and Inflammation
Wellcome Trust Principal Research Fellow
UCL Great Ormond Street Institute of Child Health
United Kingdom

At the start of the 1990s, the first clinical trials of gene therapy were attempted for an inherited severe combined immunodeficiency (SCID) caused by deficiency of the intracellular enzyme adenosine deaminase. In the absence of definitive treatment, SCID of any molecular type is usually fatal within the first year of life, although patients with ADA deficiency can be supported by administration of exogenous enzyme replacement. Even so, this is often only partially effective, and is extremely expensive. The rationale for the development of gene therapy PID therefore derives from the severity of the illness, the inadequacy of conventional therapy, and the considerable morbidity and mortality associated with stem-cell transplantation, particularly from a mismatched donor.

Although retroviruses are highly effective for gene transfer, their dependence on chromosomal integration brings a risk of inadvertent gene activation or inactivation. Reports of adverse events in several applications paved the way to the development of refined vector technologies. Clinical trials using next-generation self-inactivating gammaretroviral and lentiviral vectors have now been reported, and clearly demonstrate the huge potential of gene therapy for haematopoietic disorders including SCID-X1, Wiskott-Aldrich Syndrome, and ADA-SCID. At the same time, the safety profile appears to have been significantly enhanced, and efforts are being made to develop licensed products. New technologies including homologous recombination or gene repair to accurately correct genetic mutations may eventually supersede gene addition once limitations of efficiency and toxicity have been addressed.

 Next-Gen X – Xenogeneic generation of human organs

Pablo Juan Ross, PhD
Associate Professor, Department of Animal Science
University of California Davis
United States
Interspecies blastocyst complementation offers the possibility of generating human organs in animals. This approach requires a host embryo for which development of a specific organ is genetically disabled and human cells with interspecific chimera formation potential. Results demonstrating the utility CRISPR-Cas9-mediated zygote genome editing for creating pig and sheep organogenesis-disabled host embryos will be presented. Also, the potential of human PSCs (hPSCs) to contribute to chimera formation in livestock embryos will be addressed. Procedures and observations that will be discussed regarding the capability of human pluripotent stem cells to integrate and differentiate in an ungulate embryo may constitute a first step towards realizing the potential of interspecies blastocyst complementation for xeno-generating transplantable human tissues and organs towards addressing the worldwide shortage of organ donors.
ISCT 2017

ISCT 2017