Abstract
Current treatment for severe primary immunodeficiency diseases (PID) is not entirely satisfactory. Some patients affected with these fatal diseases can be rescued with allogeneic stem cell transplantation (SCT). This has resulted in improvement of patient survival, primarily when using HLA identical sibling or unrelated donors. In the absence of HLA identical donors patients can receive an HLA haploidentical SCT from a parent, provided donor stem cells are depleted of mature T cells that would otherwise cause lethal graft versus host disease. Despite this precaution mortality with parent donors remains high (∼50%) due to slow immune reconstitution, reactivated opportunistic infections, and immunological complications such as graft failure or rejection. Gene therapy has therefore become an attractive alternative for patients with an indication for SCT, lacking an HLA identical donor. Since protein products of PID genes are highly expressed in the hematopoietic system, addition of correct copies of the gene to hematopoietic stem cells (HSC) can be expected to restore immune function. Following recent advances in the technology of gene transfer three PID, X-linked severe combined immunodeficiency disease (X-SCID = gamma-C deficiency), Adenosinedeaminase deficient SCID (ADA-SCID), and X-linked chronic granulomatous disease (X-CGD = gp91phox deficiency) have now been corrected by ex-vivo gene transfer into hematopoietic stem cells using retroviral vectors.
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Grez, M., Stein, S., Siler, U., Seger, R. (2010). Gene Modified Hematopoietic Stem Cells for the Treatment of Primary Immunodeficiency Diseases. In: Noll, T. (eds) Cells and Culture. ESACT Proceedings, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3419-9_13
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DOI: https://doi.org/10.1007/978-90-481-3419-9_13
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