Gene and cell therapy for primary immunodeficiency diseases

Abstract

Primary immunodeficiency diseases (PID) represents a group of inherited diseases where mutations in certain gene lead to certain levels of defects in patient immune systems. Among them, several types of PID, including severe combined immunodeficiecny (SCID), warrented development of new types of curative treatment other than allogeneic hematopoietic stem cell transplantation, eventually culiminating in successful stem cell gene therapy tials such as the cases for adenosine deaminase (ADA)-deficiency SCID patients. In this article, I will summarize the current status of stem cell gene therapy for PID, and discuss the problems such clinical trials have in the present forms of treatment, e.g., possible risks of leukemogenesis due to insertional mutagenesis by the use of therapeutic viral vectors. I also try to discuss the future of this type of experimental medicine aiming for the permanent cure of PID, including the one utilizing innovative technologies such as induced pluripotent stem cells. © 2010 The Japan Society for Clinical Immunology.