Gene therapy for primary immunodeficiencies.
Thomas Andrew FoxClaire BoothPublished in: British journal of haematology (2020)
Primary immunodeficiencies (PIDs) are a group of rare inherited disorders of the immune system. Many PIDs are devastating and require a definitive therapy to prevent progressive morbidity and premature mortality. Allogeneic haematopoietic stem cell transplantation (alloHSCT) is curative for many PIDs, and while advances have resulted in improved outcomes, the procedure still carries a risk of mortality and morbidity from graft failure or graft-versus-host disease (GvHD). Autologous haematopoietic stem cell gene therapy (HSC GT) has the potential to correct genetic defects across haematopoietic lineages without the complications of an allogeneic approach. HSC GT for PID has been in development for the last two decades and the first licensed HSC-GT product for adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is now available. New gene editing technologies have the potential to circumvent some of the problems associated with viral gene-addition. HSC GT for PID shows great promise, but requires a unique approach for each disease and carries risks, notably insertional mutagenesis from gamma-retroviral gene addition approaches and possible off-target toxicities from gene-editing techniques. In this review, we discuss the development of HSC GT for PID and outline the current state of clinical development before discussing future developments in the field.
Keyphrases
- stem cell transplantation
- gene therapy
- high dose
- stem cells
- bone marrow
- genome wide
- copy number
- cardiovascular events
- risk factors
- multiple sclerosis
- type diabetes
- sars cov
- cell therapy
- big data
- mesenchymal stem cells
- crispr cas
- minimally invasive
- hematopoietic stem cell
- current status
- cardiovascular disease
- acute lymphoblastic leukemia
- acute myeloid leukemia
- adipose tissue
- locally advanced
- transcription factor
- insulin resistance
- rectal cancer
- drug induced