Operational Milestone #1

The overall objective of this CLIN1-08363 award is the completion of pre-clinical studies to generate a successful IND application and IRB approved protocol for a UCSF clinical trial of gene therapy for children with Artemis-deficient severe combined immunodeficiency (ART-SCID). This inherited immune defect causes affected patients to lack T and B lymphocytes, making them highly susceptible to life-threatening infections. It is at present the most difficult type of SCID to treat successfullly. The standard treatment for ART-SCID has been bone marrow transplantation from a healthy tissue-matched donor, but many patients lack an ideal donor. In addition, the Artemis gene defect makes ART-SCID patients more sensitive to side effects from irradiation or alkylating agent chemotherapy than other children; these agents have been given in the past to achieve engraftment of donor blood-forming stem cells in individuals with ART-SCID. Gene therapy is anticipated to overcome both problems of matching donors to patients and toxicity of high-dose chemotherapy.
We have developed a lentivirus vector carrying a correct copy of the Artemis gene with its own endogenous promotor to drive physiological levels of normal Artemis gene expression in patient blood forming bone marrow cells that receive it. To use this vector as a clinical treatment we are pursuing safety and effectiveness studies. Operational Milestone #1 of this project is to have achieved manufacture and release of the cell product (gene modified hematopoietic cells, HSC) for IND-enabling toxicity and efficacy studies utilizing a GMP-comparable lentiviral vector. At this time we have achieved this Milestone.