Laura Costa - Academia.edu (original) (raw)

Papers by Laura Costa

Expert Review of Clinical Immunology, 2005

Primary immunodeficiencies (PIDs) result from inherited mutations in genes involved in the produc... more Primary immunodeficiencies (PIDs) result from inherited mutations in genes involved in the production, function or survival of specific elements of the immune system (T, B, NK lymphocytes, neutrophils, antigen-presenting cells). Knowing that these elements derive from pluripotent hematopoietic stem cells, it has been tried to use allogeneic hematopoietic stem cell transplantation (HSCT) as an alternative for patients with a PID, which has proven to be an effective therapeutic approach leading to immune restoration. Gene therapy is an emerging strategy that bypasses some important immunological risks of allogeneic HSCT, such as complications inherent to myeloablative chemotherapy or graft-versus-host disease (GVHD), providing several additional benefits for treatment of patients with PIDs. Gene therapy is available as a treatment option for humans with ADA-SCID and SCID-X1 and, in regard to Chronic Granulomatous Disease and Wiskott-Aldrich Syndrome, while not currently available, has been attempted. Moreover, further investigation is needed before we can use gene therapy to treat humans with RAG-deficient SCID, Jak-3 deficient SCID, X-HIGM1, XLA or LAD I. Over the past years, some risks and limitations associated with the technical process behind gene therapy have been reported, such as insertional oncogenesis, which emphasizes the demand for more research in this field. In this review, we will summarize progress toward the use of gene therapy in PIDs, highlighting its advantages in comparison with HSCT. We will also address some technical aspects and limitations of the procedure behind gene therapy as well as recent strategies that aim to overcome these obstacles.

Expert Review of Clinical Immunology, 2005

Primary immunodeficiencies (PIDs) result from inherited mutations in genes involved in the produc... more Primary immunodeficiencies (PIDs) result from inherited mutations in genes involved in the production, function or survival of specific elements of the immune system (T, B, NK lymphocytes, neutrophils, antigen-presenting cells). Knowing that these elements derive from pluripotent hematopoietic stem cells, it has been tried to use allogeneic hematopoietic stem cell transplantation (HSCT) as an alternative for patients with a PID, which has proven to be an effective therapeutic approach leading to immune restoration. Gene therapy is an emerging strategy that bypasses some important immunological risks of allogeneic HSCT, such as complications inherent to myeloablative chemotherapy or graft-versus-host disease (GVHD), providing several additional benefits for treatment of patients with PIDs. Gene therapy is available as a treatment option for humans with ADA-SCID and SCID-X1 and, in regard to Chronic Granulomatous Disease and Wiskott-Aldrich Syndrome, while not currently available, has been attempted. Moreover, further investigation is needed before we can use gene therapy to treat humans with RAG-deficient SCID, Jak-3 deficient SCID, X-HIGM1, XLA or LAD I. Over the past years, some risks and limitations associated with the technical process behind gene therapy have been reported, such as insertional oncogenesis, which emphasizes the demand for more research in this field. In this review, we will summarize progress toward the use of gene therapy in PIDs, highlighting its advantages in comparison with HSCT. We will also address some technical aspects and limitations of the procedure behind gene therapy as well as recent strategies that aim to overcome these obstacles.