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T cell gene therapy to treat immunodeficiency
Author(s) -
Panchal, Neelam,
Ghosh Sujal,
Booth Claire
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17070
Subject(s) - genetic enhancement , immunology , primary immunodeficiency , immune system , immune dysregulation , immunodeficiency , stem cell , enteropathy , severe combined immunodeficiency , t cell , foxp3 , medicine , transplantation , cell therapy , hematopoietic stem cell transplantation , lymphoproliferative disorders , disease , biology , lymphoma , gene , genetics
Summary The application of therapeutic T cells for a number of conditions has been developed over the past few decades with notable successes including donor lymphocyte infusions, virus‐specific T cells and more recently CAR‐T cell therapy. 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‐modified 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‐editing 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‐Linked) due to dysfunctional FOXP3 and CTLA4 deficiency] or cytotoxicity [defective in X‐lymphoproliferative 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.