20 years of gene therapy for SCID

  title={20 years of gene therapy for SCID},
  author={Alain Fischer and Salima Hacein-Bey-Abina and Marina Cavazzana‐Calvo},
  journal={Nature Immunology},
Severe combined immunodeficiency conditions are devastating disorders of adaptive immunity. Although these diseases were initially treated by transplantation of allogeneic hematopoietic stem cells, the past 20 years has shown that these conditions are correctable by gene therapy. 

Gene therapy finds its niche

Gene therapy is finally poised to make a contribution to the treatment of debilitating, highly penetrant genetic diseases that have proved intractable to other regimens.

A single‐center study of hematopoietic stem cell transplantation for primary immune deficiencies (PIDD)

A single‐center study of hematopoietic stem cell transplantation for primary immune deficiencies (PIDD) and its effects on survival and quality of life is presented.

Gene therapy for Wiskott-Aldrich Syndrome—Long-term reconstitution and clinical benefits, but increased risk for leukemogenesis

Wiskott-Aldrich-Syndrome is a rare X-linked recessive disease caused by mutations of the WAS gene that is characterized by immunodeficiency, autoimmunity, low numbers of small platelets and a high risk of cancer, especially B cell lymphoma and leukemia.

Haematopoietic stem cell transplantation for SCID patients: where do we stand?

The complete absence of the T cell compartment in SCID prompted the development of haploidentical, parental HSCT for the many patients who do not have a human leucocyte antigen (HLA)‐identical sibling.

Gene Therapy for Primary Immunodeficiencies

Clinical trials for SCID-X1, Wiskott-Aldrich syndrome, and recently ADA-SCID showed sustained engraftment of gene-corrected cells, restored immune function, and general improvement of clinical condition, with a positive safety profile, so continuous monitoring will be important to confirm long-term safety and efficacy.

Gene therapy for primary immunodeficiencies

Results of recent trials performed for several forms of PID suggest that their use is both safe and efficacious, and it is anticipated that their application to the treatment of many more life threatening PID will be developed over the coming years.

Homologous recombination‐based gene therapy for the primary immunodeficiencies

  • M. Porteus
  • Biology, Medicine
    Annals of the New York Academy of Sciences
  • 2011
The development of nuclease‐stimulated, homologous recombination‐based approaches as a novel gene therapy strategy for the primary immunodeficiencies is discussed.

Hematopoietic stem cell expansion and gene therapy.

Some of the current limitations of HSC gene therapy could be overcome by combining novel HSC expansion strategies with gene therapy, as well as the opportunities presented by implementing ex vivo expansion of gene-modified HSC.

Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency

In comparison with SCID-X1, ADA-SCID gene therapy presents a better safety profile and engraftment of multilineage transduced stem/progenitor cells, thanks to the use of nonmyeloablative preconditioning.



Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning

Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions, and lower toxic metabolites, indicating the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID.

T Lymphocyte-Directed Gene Therapy for ADA− SCID: Initial Trial Results After 4 Years

It is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Gene therapy for immunodeficiency due to adenosine deaminase deficiency.

Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency and effective protection against infections and improvement in physical development made a normal lifestyle possible.

Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy.

Ex vivo gene therapy with gamma(c) can safely correct the immune deficiency of patients with X-linked severe combined immunodeficiency and allow patients to have a normal life.

Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.

A gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells, which provided full correction of disease phenotype and clinical benefit.

Gene therapy: A tragic setback

With one French gene-therapy patient having developed a form of cancer, a frantic detective effort is under way to determine what went wrong — and to assess the risks faced by others. Erika Check

LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1

Retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

Lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD, and progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT.

How I treat ADA deficiency.

The choice between ERT, MUD transplant, or GT is difficult and dependent on several factors, including accessibility to the different modalities, response of patients to long-term ERTs, and the attitudes of physicians and parents to the short- and potential long- term risks associated with different treatments.