Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders
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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.
KeywordsPrimary immunodeficiency Cytotoxic T lymphocytes Adoptive immunotherapy Antiviral therapy Hematopoietic stem cell transplantation
We would like to thank the staffs of the Divisions of Allergy and Immunology and Blood and Marrow Transplantation at Children’s National Medical Center, our collaborators at the Cell and Gene Therapy center at Baylor College of Medicine and other institutions, the Children’s Research Institute, and the Jeffrey Modell Foundation for their support of this work.
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Conflict of Interest
Drs. McLaughlin, Bollard, and Keller declare no conflicts of interest relevant to this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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