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Primary immunodeficiencies are monogenetic disorders leading to abnormal development or function of the immune system. Haematopoietic stem cell transplantation and, in specific candidate diseases, haematopoietic stem cell gene therapy has been the only definitive treatment option so far. However, autologous gene\u2010modified T cell therapy may offer a potential cure in conditions primarily affecting the lymphoid compartment. In this review we will highlight several T cell gene addition or gene\u2010editing approaches in different target diseases with a focus on what we have learnt from clinical experience and promising preclinical studies in primary immunodeficiencies. Functional T cells are required not only for normal immune responses to infection (affected in CD40 ligand deficiency), but also for immune regulation [disrupted in IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X\u2010Linked) due to dysfunctional FOXP3 and CTLA4 deficiency] or cytotoxicity [defective in X\u2010lymphoproliferative disease and familial haemophagocytic lymphohistiocytosis (HLH) syndromes]. In all these candidate diseases, restoration of T cell function by gene therapy could be of great value.<\/jats:p>","DOI":"10.1111\/bjh.17070","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T14:03:22Z","timestamp":1600956202000},"page":"433-443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["T cell gene therapy to treat immunodeficiency"],"prefix":"10.1111","volume":"192","author":[{"given":"Neelam","family":"Panchal,","sequence":"first","affiliation":[{"name":"Molecular and Cellular Immunology Section UCL Great Ormond Street Institute of Child Health London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujal","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology Medical Faculty Center of Child and Adolescent Health Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2626-5037","authenticated-orcid":false,"given":"Claire","family":"Booth","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Immunology Section UCL Great Ormond Street Institute of Child Health London UK"},{"name":"Department of Paediatric Immunology Great Ormond Street Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00758-x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00295"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz170"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.12.1311"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2018.10.049"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000924"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30823-X"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.001"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0297-y"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050016058"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.7.1988.1988"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380050202"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-1248-2_22"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00314"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526248"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001770"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.12.009"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-189209"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070104"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0502-423"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010314"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2009.1.682"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2800"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5235.475"},{"key":"e_1_2_7_26_1","unstructured":"BlaeseRM CulverKW ChangL AndersonWF MullenC NienhuisA et al.Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. 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