Year 1

The HIV-1 virus enters cells by binding to a protein called CCR5 on the cell surface. A naturally occurring mutation in CCR5, CCR532, has been shown to provide protection from HIV-1 infection and AIDS. Media and scientific magazines have discussed widely the case of the “Berlin patient,” who was cured of his HIV-1 infection after receiving therapy for his leukemia with a blood stem cell transplant from a donor whose cells had both copies of CCR5 mutated. This strategy is unlikely to be successful for the AIDS patient in general since donors must be a near-perfect tissue match with the patient and also have the double CCR5 mutation, two rare events which almost never happen together.

To mimic the effect of the CCR5 double mutation, this project creates blood stem cells that have a double mutation in the CCR5 gene and then test this gene therapy method in HIV-infected research participants. The participants’ own blood stem cells are treated in a process that can mutate the CCR5 gene, and then the stem cells are infused back into the individual. These cells carry the disrupted CCR5 gene. We administer a low dose of chemotherapy called busulfan to the recipient prior to the transplant to provide space for the new stem cells. We anticipate 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 gets around the need to find a stem cell donor who carries the CCR5 double mutation and, since the stem cells come from the patient, there will be an ideal “perfect match” with no chance for rejection in the patient.

The applicant institution has worked with collaborating partners to start the study in July 2015. Three participating clinics screen and enroll the eligible participants. So far, we have enrolled the first research participant and have successfully mobilized and collected the blood stem cells and have manufactured the gene-modified blood stem cells. We are now in the process of testing of this investigational product. Screening of potential participants continues at the clinics currently open to recruitment. It is planned to add more clinics to the study in the current funding year.

This is a partnership among City of Hope, Sangamo Biosciences 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.