Operational Milestone #4 or 4b

The goal of this study is to test in patients if a protein (antibody) that targets a molecule called CD117 can safely and effectively deplete recipient blood stem cells, and thereby permit donor blood stem cells to engraft in children with severe combined immunodeficiency (SCID), also known as the bubble boy disease.  These children cannot survive without a blood stem cell transplant, but doctors rely on toxic chemotherapy to get donor blood stem cells to permanently engraft.  Hence, the procedure can cause unwanted complications due to the chemotherapy, or if no chemotherapy is given before the infusion of donor stem cells, results can be suboptimal.  Until now, no safe biologic agent existed to prepare patients for transplant. 

This Disease Team has achieved the major goals of translating the discovery first made in mice of using anti-CD117 antibodies to achieve stem cell engraftment, to the current open clinical trial in children with SCID.  To date we have transplanted nine patients using the anti-CD117 to prepare patients to accept the donor cells, and all patients tolerated the procedure well without side effects. This clinical study is testing three increasing doses in patients who are treated in groups of three.  The operational milestone (OM) that was recently achieved was to transplant the 9th patient.  Remarkably, the trial started with very low doses of the antibody, and even at low doses, the study patients are showing benefit in the form of engraftment of stem cells and regeneration of lymphocytes from the donor stem cells. In those patients who are far out enough from transplant to assess possible benefit, these regenerating lymphocytes show evidence that they are protecting the transplanted patients from infectious diseases.  

During the last study period we performed the following: (1) continued enrollment and treatment of new SCID patients on the clinical study; (2) continued to monitor the patients who have been treated on this study to date; (3) worked to open a third clinical treating site so that we can reach more patients with this treatment; (4) continued to manage the supply of anti-CD117 antibody to ensure its availability for the current clinical trial; and (5) met with the FDA to discuss design of future clinical trials that will allow the development of anti-CD117 to become a commercial product that can be more broadly used for patients with SCID and other diseases for whom blood stem cell transplantation is indicated.