Final Program - American Society of Gene & Cell Therapy

Program Schedule, Wednesday, May 15, 2013
Wednesday, May 15, 2013
Education Session 113
10:30 am - 12:00 pm
ROOM: 150 DEFG
Topical Review: Gene and Cell Therapy Approaches to Hemoglobinopathies
This session will introduce basic, translational and clinical efforts to provide therapeutic advances for the two major Hemoglobinopathies:
sickle-cell anemia (SCD) and beta-thalassemia’s using gene therapy approaches. Elevation of HbF production has been a long-standing
goal of therapy for ß-thalassemia and sickle cell disease (SCD) as its expression provides a potent attenuation of many of the most severe
complications of disease phenotype. The central theme of this session will be improving gene transfer and gene correction in human
hematopoietic stem and progenitor cells to provide more effective and safe therapies for blood cell disorders. In addition, efforts and the
lessons learnt from gene therapy of Severe Combined Immunodeiciency (SCID) disease.
CO-CHAIRS: Pankaj Qasba, PhD and Sonia I. Skarlatos, PhD
SPEAKERS
Punam Malik, MD, PhD
Gene and Cell Therapy Approaches to Hemoglobinopathies
Dr. Malik will present an overview of genetic therapies for hemoglobiniopathies, a review of the literature, the current state of the
ield and future promising ways of gene editing and reprogramming.
John F. Tisdale, MD
Stem Cells as Gene Therapy Vehicles for the Treatment of Disorders of Globin Synthesis
Sickle cell disease (SCD) is a recessive genetic disease that results from the production of an abnormal hemoglobin that is prone
to polymerization upon deoxygenation causing severe morbidity and early mortality. Although palliative therapies have been
developed, conventional treatment remains unsatisfactory. Signiicant advances in cellular and molecular biology have enabled
the development of a mounting armamentarium of tools to allow correction at the hematopoietic stem cell (HSC) level. Allogeneic
HSC transplantation, a form of genetic therapy, is an established curative approach through replacement of the defective organ
with that of a donor carrying the normal genotype; however, procedural toxicities limit this approach to only severely affected
children. Nonmyeloablative approaches based upon basic and preclinical studies have now allowed for the successful application
of this approach in adults with severe disease, with disease reversion in the majority of patients treated through the attainment of
stable mixed hematopoietic chimerism. Nonetheless, this approach remains limited by donor availability, and the development of
gene transfer directed at autologous HSCs remains a desirable alternative. Approaches using autologous transplantation of HSCs
modiied by lentiviral vectors have demonstrated expression of the human beta-globin protein at clinically signiicant levels, and
this approach is now being developed for clinical application in SCD. The progress toward the goal of these HSC based therapies will
be reviewed.
Donald B. Kohn, MD
Lessons Learned from Gene Therapy for SCID
The implementation and performance of clinical trials of gene therapy using hematopoietic stem cells is a complex process. After
proof-of-principle studies demonstrate potential disease modifying activity, preclinical activity and toxicology data need to be
generated, along with clinical protocol, consent documents, etc. to support regulatory applications. Subjects are treated in the
high acuity setting of hematopoietic stem cell transplantation (HSCT) which may include the use of myeloreductive conditioning,
although no immune suppression pre- or post-transplant is needed, due to the use of autologous cells. Ultimately, clinical
acceptance of gene therapy as a standard of care will depend on demonstrating equivalent or greater eficacy and improved
outcomes or reduced costs, compared to allogeneic HSCT. Experience with gene therapy for severe combined immune deiciency
may inform efforts to develop similar approaches to hemoglobinopathies; persistence and patience are needed.
Education Session 114
10:30 am - 12:00 pm
ROOM: 151 ABCG
Topical Review: Vector Design
CO-CHAIRS: Alberto Auricchio, MD and Dirk Grimm, PhD
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Final Program SALT LAKE CITY, UTAH May 15–18, 2013