OM #2

This clinical project aims to create blood stem cells that have a disrupted CCR5 gene, which can no longer produce a protein used by the HIV-1 virus to enter the cells. The blood cells derived from these stem cells would then be protected from HIV infection. The goal is to test the safety and feasibility of this gene therapy method in HIV-infected research participants. The participants’ own blood stem cells are collected and then treated in a process that can attack the CCR5 gene, and then the stem cells are infused back into the individual. To assure that these cells find a place to grow in the bone marrow of the recipient, a low dose of chemotherapy called busulfan is given to the recipient prior to infusion of the CCR5-modified stem cells. It is anticipated that, upon stem cell infusion, the gene-modified cells will provide a renewable, long-lasting source of HIV-1 resistant immune cells. This novel strategy tries to achieve the results seen with the publicized case of the “Berlin patient.” This patient was cured of his HIV-1 infection after receiving therapy for his leukemia with a blood stem cell transplant from a donor who inherited disrupted CCR5 genes.
The applicant institution has worked with collaborating partners to start the study in July 2015. Six participating clinics screen and enroll the eligible participants. The first 3 research participants have had the gene-modified blood stem cells manufactured and successfully treated with this product after low dose chemotherapy. With this, the first milestone for this project was achieved. With the infusion of the fourth research participant after higher dose chemotherapy, the second milestone has been achieved. The progress advances with continued enrollment of more patients into the study with the goal of achieving the next milestone, the treatment of the ninth participant.
This is a partnership among City of Hope, Sangamo Therapeutics Inc, and CIRM. With combined expertise in stem cells, gene therapy, transplantation, treatment of HIV-related disease, this Strategic Partnership has the knowledge, skill and resources to achieve all project goals.