Tags

Type your tag names separated by a space and hit enter

Ten years of gene therapy for primary immune deficiencies.

Abstract

Gene therapy with hematopoietic stem cells (HSC) is an attractive therapeutic strategy for several forms of primary immunodeficiencies. Current approaches are based on ex vivo gene transfer of the therapeutic gene into autologous HSC by vector-mediated gene transfer. In the past decade, substantial progress has been achieved in the treatment of severe combined immundeficiencies (SCID)-X1, adenosine deaminase (ADA)-deficient SCID, and chronic granulomatous disease (CGD). Results of the SCID gene therapy trials have shown long-term restoration of immune competence and clinical benefit in over 30 patients. The inclusion of reduced-dose conditioning in the ADA-SCID has allowed the engraftment of multipotent gene-corrected HSC at substantial level. In the CGD trial significant engraftment and transgene expression were observed, but the therapeutic effect was transient. The occurrence of adverse events related to insertional mutagenesis in the SCID-X1 and CGD trial has highlighted the limitations of current retroviral vector technology. For future applications the risk-benefit evaluation should include the type of vector employed, the disease background and the nature of the transgene. The use of self-inactivating lentiviral vectors will provide significant advantages in terms of natural gene regulation and reduction in the potential for adverse mutagenic events. Following recent advances in preclinical studies, lentiviral vectors are now being translated into new clinical approaches, such as Wiskott-Aldrich Syndrome.

Authors+Show Affiliations

San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20008254

Citation

Aiuti, Alessandro, and Maria Grazia Roncarolo. "Ten Years of Gene Therapy for Primary Immune Deficiencies." Hematology. American Society of Hematology. Education Program, 2009, pp. 682-9.
Aiuti A, Roncarolo MG. Ten years of gene therapy for primary immune deficiencies. Hematology Am Soc Hematol Educ Program. 2009.
Aiuti, A., & Roncarolo, M. G. (2009). Ten years of gene therapy for primary immune deficiencies. Hematology. American Society of Hematology. Education Program, 682-9. https://doi.org/10.1182/asheducation-2009.1.682
Aiuti A, Roncarolo MG. Ten Years of Gene Therapy for Primary Immune Deficiencies. Hematology Am Soc Hematol Educ Program. 2009;682-9. PubMed PMID: 20008254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ten years of gene therapy for primary immune deficiencies. AU - Aiuti,Alessandro, AU - Roncarolo,Maria Grazia, PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/3/17/medline SP - 682 EP - 9 JF - Hematology. American Society of Hematology. Education Program JO - Hematology Am Soc Hematol Educ Program N2 - Gene therapy with hematopoietic stem cells (HSC) is an attractive therapeutic strategy for several forms of primary immunodeficiencies. Current approaches are based on ex vivo gene transfer of the therapeutic gene into autologous HSC by vector-mediated gene transfer. In the past decade, substantial progress has been achieved in the treatment of severe combined immundeficiencies (SCID)-X1, adenosine deaminase (ADA)-deficient SCID, and chronic granulomatous disease (CGD). Results of the SCID gene therapy trials have shown long-term restoration of immune competence and clinical benefit in over 30 patients. The inclusion of reduced-dose conditioning in the ADA-SCID has allowed the engraftment of multipotent gene-corrected HSC at substantial level. In the CGD trial significant engraftment and transgene expression were observed, but the therapeutic effect was transient. The occurrence of adverse events related to insertional mutagenesis in the SCID-X1 and CGD trial has highlighted the limitations of current retroviral vector technology. For future applications the risk-benefit evaluation should include the type of vector employed, the disease background and the nature of the transgene. The use of self-inactivating lentiviral vectors will provide significant advantages in terms of natural gene regulation and reduction in the potential for adverse mutagenic events. Following recent advances in preclinical studies, lentiviral vectors are now being translated into new clinical approaches, such as Wiskott-Aldrich Syndrome. SN - 1520-4383 UR - https://www.unboundmedicine.com/medline/citation/20008254/Ten_years_of_gene_therapy_for_primary_immune_deficiencies_ L2 - https://ashpublications.org/hematology/article-lookup/doi/10.1182/asheducation-2009.1.682 DB - PRIME DP - Unbound Medicine ER -