title: Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders.
abstract: Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.
authors.affiliation: Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, USA.|Division of Blood and Marrow Transplantation, Children's National Health System, Washington, DC, USA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: McLaughlin
authors.affiliation: Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, USA.|Division of Blood and Marrow Transplantation, Children's National Health System, Washington, DC, USA.|Division of Allergy/Immunology Center for Cancer and Immunology Research Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Disorders, Children's National Health System, 111 Michigan Ave NW, M7745A, Washington, DC, 20010, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.affiliation: Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, USA. MKeller@childrensnational.org.|Division of Allergy/Immunology Center for Cancer and Immunology Research Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Disorders, Children's National Health System, 111 Michigan Ave NW, M7745A, Washington, DC, 20010, USA. MKeller@childrensnational.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Keller
mesh_terms: D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D019172:Transplantation Conditioning / Q000379:methods
keywords: Adoptive immunotherapy; Antiviral therapy; Cytotoxic T lymphocytes; Hematopoietic stem cell transplantation; Primary immunodeficiency