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City of Hope’s stem cell treatment shows promise against AIDS
DUARTE, Calif. —Working with four lymphoma patients whose bone marrow had been killed via chemotherapy, a team led by Dr. David DiGuisto, director of haematopoietic cell therapies at City of Hope Medical Center in Duarte, Calif., has demonstrated promising results from subsequent treatment with genetically altered stem cells. The scientists are planning further research to establish whether the treatment might rid patients of HIV infection altogether.
The technique involves introducing genes that curb the spread of HIV inside the body into human stem cells, then transplanting the stem cells into a patient's bone marrow. In the first human trial, anti-HIV stem cells were transplanted into the four AIDS patients undergoing bone marrow replacement as part of treatment for lymphoma. The stem cells, DiGuisto says, are a mixture of genetically altered cells and "a sufficient dose of unmanipulated stem cells." The protocol calls for no less than 2 million cells per kilogram of body weight. "Our best estimate," DiGuisto adds, "is that about one percent of the cells are of the genetically altered type." All four infused patients are in remission for lymphoma with no recurrence of HIV.
Presenting his finds from the trial at the Stem Cell World Congress in Palm Springs, Calif., DiGuisto described his work as "A first-in-humans study of safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentiviral vector encoding multiple anti-HIV RNAs." Unanswered at this time is the fate of the 99 percent of the stem cells that were infused without the protecting treatment. The hope is that, in a sort of "survival of the fittest" at the cellular level, the treated stem cells will proliferate and take over.
"We are currently doing two things to improve the process," DiGuisto says. "First, we are seeking approval of a protocol to introduce 100 percent of the modified stem cells. A second approach would be to introduce the same modified genes into T-lymphocytes of HIV patients. We have data to show that the resistant cells are persisting in our lymphoma patients. It is still an experimental treatment, but we hope that eventually we will be able to give AIDS patients just one transplant that would protect them for life."
The next step is to repeat the first-in-human trial in five to 10 patients, DiGuisto adds, and then to increase the cohort to between 30 and 50 individuals.
Around 40 million people worldwide are infected with HIV and an estimated three million die each year with the virus. HIV attacks white blood cells known as T-lymphocytes, which play a central role in the immune system by fighting infection.
City of Hope is one of 40 National Cancer Institute-designated Comprehensive Cancer Centers nationwide and a founding member of the National Comprehensive Cancer Network. An independent biomedical research, treatment and education institution, it is dedicated to the mission of conquering cancer, diabetes, HIV/AIDS and other life-threatening diseases. DDN