Standing on the Shoulders of Stem Cell Gene Therapists: History, Hyperbole, and Hope for the Future.

Abstract

A new type of medicine approved in Europe at the end of May represents the culmination of the successful convergence of two fields of science: stem cell transplantation and gene therapy. Strimvelis, a patient-specific gene-modified stem cell medicine for ADA-SCID (adenosine deaminase deficiency leading to severe combined immunodeficiency; a fatal immunometabolic disorder similar to the bubble-boy disease), was developed by scientists at the San Raffaele Telethon Institute for Gene Therapy (TIGET) in Milan, Italy, which then later partnered with GlaxoSmithKline (GSK, Brentford, UK). The journey took more than 25 years of dedicated work by many groups and involved a pivotal trial with 12 children and their brave families. I was fortunate to be involved on the GSK side of the TIGET alliance from 2010 to 2015, building on my previous experiences with gene-modified stem cells during a postdoctoral fellowship in the mid-1990s and at Chiron, which had acquired Viagene, an early gene therapy biotech firm. I thought it was timely to pick out a couple of observations from the development of Strimvelis, to see how these might apply to the future of stem cell gene therapy and perhaps act like shoulders for the related chimeric antigen receptor T-cell (CAR-T) and gene-editing technologies to stand on.