title: Cellular therapy for sickle cell disease.
abstract: Sickle cell disease (SCD) is a monogenic red cell disorder affecting more than 300 000 annual births worldwide and leading to significant organ toxicity and premature mortality. Although chronic therapies such as hydroxyurea have improved outcomes, more durable therapeutic and curative options are still being investigated. Newer understanding of the disease has implicated invariant natural killer T cells as a critical immune profile that potentiates SCD. Hence, targeting this cell population may offer a new approach to disease management. Hematopoietic stem cell transplant is a curative option for patients with SCD, but the under-representation of minorities on the unrelated donor registry means that this is not a feasible option for more than 75% of patients. Work in this area has therefore focused on increasing the donor pool and decreasing transplant-related toxicities to make this a treatment option for the majority of patients with SCD. This review focuses on the currently available cell and gene therapies for patients with SCD and acknowledges that newer gene-editing approaches to improve gene therapy efficiency and safety are the next wave of potentially curative approaches.
authors.affiliation: Division of Blood and Marrow Transplant, Children's National Health System and The George Washington University, Washington, DC, USA; Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington, DC, USA. Electronic address: aabraham@childrensnational.org.
authors.forename: Allistair
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Division of Blood and Marrow Transplant, Children's National Health System and The George Washington University, Washington, DC, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Jacobsohn
authors.affiliation: Division of Blood and Marrow Transplant, Children's National Health System and The George Washington University, Washington, DC, USA; Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington, DC, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
mesh_terms: D000755:Anemia, Sickle Cell / Q000628:therapy*; D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D055611:Natural Killer T-Cells / Q000276:immunology
keywords: gene therapy; hematopoietic stem cell transplant; sickle cell anemia; sickle cell disease