Session Details

Plenary Session 2 – iPSC and Pluripotent Stem Cells - True Replacement Cell Therapies
Friday, September 13, 2019 01:45 PM - 03:15 PM
Plenary Hall
Pluripotent stem cells in combination with advanced genome engineering tools can be the manufacturing platform for future cell therapies.  This is being realized through translational studies in immunotherapy (NK cells), the brain (dopaminergic neurons) and heart disease (pacemakers and ventricular cardiomyocytes).  

Chair: Robert Deans, PhD, BlueRock Therapeutics, USA

Engineered iPSC-derived Lymphocytes for Improved Cancer Therapy
Dan Kaufman, MD, PhD, University of California San Diego, USA
Human pluripotent stem cells provide a novel source for cellular immunotherapies. Specifically, natural killer (NK) cells can be efficiently derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). hESCs and iPSCs serve as a platform for genetic modifications to express chimeric antigen receptors and other strategies to enhance anti tumor activity. Our group has demonstrated expression of novel NK cell specific CARs function better in NK cells than standard T cell CAR constructs. Additional modifications include expression of a high affinity, non cleavable version of the Fc receptor CD16 to enhance antibody mediated killing of tumor cells. We have also introduced an IL 15RF fusion transgene was to provide self stimulating signals to support NK cell function and persistence. Internal genes can be edited via CRISPR/Cas9 to improve NK cell function. Importantly, iPSC derived NK cells can be expanded to clinical scale in GMP compatible conditions. Since NK cells function as allogeneic cells, this strategy enables use of iPSC derived NK cells as an “off the shelf” targeted cellular immunotherapy against refractory malignancies.

Cell replacement therapy for the conduction system: biological pacemakers
Stephanie Protze, PhD, University of Toronto, Canada
The conduction system of the heart consists of the primary pacemaker (sinoatrial node, SAN), the secondary pacemaker (atrioventricular node, AVN) and specialized conduction fibers (His-purkinje system) that regulate the heartbeat throughout life. Failure of any part of the conduction system results in an irregular/slow heart rate and inefficient blood circulation, a condition treated by implantation of an electronic pacemaker. The ability to produce pacemaker cells in vitro could lead to an alternative, biological pacemaker therapy in which the failing part of the conduction system is replaced through cell transplantation. Pluripotent stem cells represent an ideal source for the generation of genuine pacemaker cells. We established developmental biology guided protocols for the specification of SAN-like pacemaker cells (SANLPCs) that closely resemble the primary pacemaker of the heart. SANLPCs are identified as NKX2-5 negative cardiomyocytes that express typical markers of the SAN lineage and display typical pacemaker action potentials, ion current profiles and chronotropic responses. Importantly, when transplanted into the apex of rat hearts, SANLPCs are able to pace the host tissue, demonstrating their capacity to function as a biological pacemaker. We are currently establishing a pig model to test the long-term reliability and safety of SANLPC comprised biological pacemakers.

Cell Therapy for the Brain: Neuronal and Glial based Therapeutics
Robert Deans, PhD, BlueRock Therapeutics, USA
Parkinson’s disease is the hallmark of degenerative CNS pathology, and severely limited from a cell therapeutics approach.  iPSC are a platform for derivation of dopaminergic neurons as a cell replacement therapy and pre-clinical studies supporting an IND for treatment will be discussed.  This platform includes the production of other brain cells useful for cell replacement therapy, notably all classes of neurons, oligodendrocytes for demyelinating disease, and microglia for neuroinflammatory disease.  The ability to gene edit to enable allogeneic cell use, as well as to augment potency for diseases such as lysosomal storage disorders, completes a powerful toolbox for creation of next generation cellular medicines for the brain.