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Gene Therapy in Cellular Immunodeficiencies

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Cellular Primary Immunodeficiencies

Part of the book series: Rare Diseases of the Immune System ((RDIS))

Abstract

The treatment of cellular primary immunodeficiencies has benefitted from significant advances in the field of allogeneic stem cell transplantation (alloHSCT). However, while this therapy is curative for many PIDs, the procedure requires a suitably matched donor and carries significant risks of morbidity and mortality from complications such as graft-versus-host disease (GVHD). Autologous gene therapy (GT) approaches using stem cells isolated from patients and modified ex vivo using viral vectors or gene editing techniques have the potential to offer curative therapy for PID without the immunological complications of alloHSCT. GT for PID has been developed over the last 30 years, and while several setbacks have been encountered along the way, there is now a licensed GT product for ADA-SCID, and promising results from phase I/II clinical trials have demonstrated that GT may offer clinical efficacy comparable to alloHSCT in several other PIDs. Developments in the field are broadening the application of GT, and we expect that this therapeutic modality may become standard of care for the management of several PIDs in the near future. This chapter explores the development of GT over the last 30 years and outlines its role in the management of cellular primary immunodeficiencies.

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Authors and Affiliations

  1. UCL Institute of Immunity & Transplantation, University College London, London, UK

    Tom Fox & Emma C. Morris

  2. Department of Clinical Haematology, University College London Hospitals NHS Foundation Trust, London, UK

    Tom Fox & Emma C. Morris

  3. Molecular and Cellular Immunology Section, UCL GOS Institute of Child Health, London, UK

    Claire Booth

  4. Department of Paediatric Immunology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, London, UK

    Claire Booth

  5. Department of Immunology, Royal Free London Hospital NHS Foundation Trust, London, UK

    Emma C. Morris

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  1. Tom Fox
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  1. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Mario Milco D'Elios

  2. Department of Life Sciences, University of Siena, Siena, Italy

    Cosima Tatiana Baldari

  3. Department of Experimental and Clinical Medicine, University of Florence, Firenze, Florence, Italy

    Francesco Annunziato

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Fox, T., Booth, C., Morris, E.C. (2021). Gene Therapy in Cellular Immunodeficiencies. In: D'Elios, M.M., Baldari, C.T., Annunziato, F. (eds) Cellular Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-030-70107-9_19

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