Update on gene therapy of inherited immune deficiencies.
Gene therapy has been under development as a way to correct inborn errors for many years. Recently, patients with two forms of inherited severe combined immunodeficiency (SCID), adenosine deaminase and X-linked, treated by three different clinical investigative teams, have shown significant immune reconstitution leading to protective immunity. These advances irrefutably prove the concept that hematopoietic progenitor cell gene therapy can ameliorate these diseases. However, due to proviral insertional oncogenesis, two individuals in one of the X-SCID studies developed T-cell leukemia more than two years after the gene transfer. Depending upon the results of long-term follow-up, the successes together with the side effects highlight the relative merits of this therapeutic approach.
Engel
Barbara C
BC
Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA. bengel@chla.usc.edu
Kohn
Donald B
DB
Podsakoff
Greg M
GM
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000628:therapy; D015316:Genetic Therapy; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000151:congenital* / Q000235:genetics / Q000628:therapy*; D008661:Metabolism, Inborn Errors
D018952:Antigens, CD34; D000243:Adenosine Deaminase