Marina Cavazzana-Calvo, ^*123 Salima Hacein-Bey, ^*123 Geneviève de Saint Basile, ¹ Fabian Gross, ² Eric Yvon, ³ Patrick Nusbaum, ² Françoise Selz, ¹ Christophe Hue, ¹² Stéphanie Certain, ¹ Jean-Laurent Casanova, ¹⁴ Philippe Bousso, ⁵ Françoise Le Deist, ¹ Alain Fischer ¹²⁴

Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the c cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective c Moloney retrovirus-derived vector and ex vivo infection of CD34⁺ cells. After a 10-month follow-up period, c transgene-expressing T and NK cells were detected in two patients. T, B, and NK cell counts and function, including antigen-specific responses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinical benefit.

¹ INSERM Unit 429,
² Gene Therapy Laboratory,
³ Cell Therapy Laboratory,
⁴ Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker, 75743 Paris Cedex 15, France.
⁵ INSERM Unit 277, Institut Pasteur, 75730 Paris, France.
^*   These authors contributed equally to this work.

   To whom correspondence should be addressed at INSERM Unit 429, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France. E-mail: fischer{at}necker.fr