Twenty Years of Gene Therapy for Children with SCID

Event Details

Type

Friday Lecture Series

Speaker(s)

Alain Fischer, M.D., Ph.D., Professor, College de France

Speaker bio(s)

The first successful gene therapy led to correction, in a sustained manner, i.e. 20 years of the T cell immunodeficiency observed in two forms of severe combined immunodeficiency (SCID), SCID X1 the ADA deficiency. This is explained by the fact that transduction of a small number of progenitor cells led to massive expansion of T cell precursors that differentiated into long-lived mature T cells. Actually, this scenario was anticipated from the observation of partial natural correction of SCID explained by reversion. An order of magnitude of 1,000 retrovirally transduced T cell precursors was shown to generate a fully diversified T cell repertoire that is stable over time. The first generation of vectors used was based on LTR-driven transgene expression, its usage led to genotoxicity as observed in some patients. Therefore, a second generation of vectors was generated in which the transgene is placed under the control of the EF1a(s) promoter and the enhancer element of the LTR removed. Utilization of such vectors-designated self-inactivating (SIN) led to both efficacious and safe correction of SCID X1 and other diseases with a follow up that now extends over 10 years.

Lentiviral vectors that transduce hematopoietic stem cells are now in use to treat SCID but also the Wiskott-Aldrich syndrome and other immunodeficiencies (ID). Worldwide, more than 200 ID patients have now benefited from gene therapy. Altogether, gene therapy over the last 20 years, albeit through a painful way, has demonstrated its capacity to benefit patients with ID and has now entered into their therapeutic armamentarium.

Dr. Alain Fischer studied medicine, with a specialization in pediatrics and immunology at the Université of Paris. After completing a postdoctoral fellowship at the University College London, he started independent research in an INSERM unit at the Necker Hospital in Paris. From 2009 to 2016, he was the director of the Institute for Genetic Diseases (Imagine) at Necker University Hospital. Dr. Fischer also served as a professor of pediatric immunology at the Université Paris Descartes. From 1996 to 2012, he has served as the director of the pediatric immunology department at the Necker Hospital. Dr. Fischer is presently Professor at College de France. Dr. Fischer's main research interests are gene therapy, primary immunodeficiency diseases, and the development of the lymphoid system. Dr. Fischer received the Louis Jeantet Prize for Medicine in 2001 and the Japan Prize 2015.

Open to

Public

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Justin Sloboda

Phone

(212) 327-7785

Sponsor

Justin Sloboda
(212) 327-7785
jsloboda@rockefeller.edu