by Kathleen O’Neil
Patients with HIV-related lymphoma could soon get a new stem-cell treatment — developed in part at City of Hope — that will attempt to knock down virus levels while eradicating the cancer.
Scientists presented the research at the 48th annual meeting of the American Society of Hematology in Orlando, Fla., in December.
The treatment would be the first to use specially engineered, HIV-fighting genes that are inserted into patients’ own stem cells. The cells would then be reinfused into HIV-infected patients during a bone marrow transplant. If successful, the new treatment could allow patients’ bodies to produce HIV-resistant white blood cells indefinitely.
“This may be a way to control the patients’ HIV while still allowing them to have a successful bone marrow transplant to treat their cancer,” said John Zaia, M.D., chair of the Department of Virology at City of Hope and an investigator in the pilot study. “It’s especially exciting because if the method using stem cells works, it could be applied to many hematological diseases that have a genetic basis.”
Zaia also presented plans at the meeting for an upcoming trial at City of Hope that would incorporate the anti-HIV therapy.
Previous research at City of Hope and other institutions has found that HIV-infected patients can tolerate and benefit from autologous stem cell transplants, which are now standard therapy for lymphoma that cannot be cured by regular-dose chemotherapy alone.
Zaia presented additional data during the conference that demonstrated the continued success of autologous transplants in HIV-infected patients who are on highly active antiretroviral therapy, a potent combination of anti-HIV drugs. City of Hope has performed autologous stem cell transplants on 28 HIV-positive patients with lymphoma since 1998.
Autologous stem cell transplants involve harvesting stem cells from a patient’s blood, then re-infusing the cells into the patient after cancerous cells have been destroyed.
The new stem cells can then develop into white blood cells, immune cells that form the body’s line of defense. The constant destruction and production of immune cells in response to HIV is one reason HIV-positive people develop lymphomas at a much higher rate than uninfected people. Lymphomas are cancers of the lymphatic system, the network of lymph ducts and nodes where immune cells circulate.
City of Hope and the Food and Drug Administration have not yet completed review of the proposed study. Upon study approval, the stem cells of patients with HIV lymphoma would undergo an additional step beyond traditional transplantation: the insertion of anti-HIV gene segments into the cells before they are reinfused into the body. Scientists use a lentivirus to carry the gene segments (in the form of RNA) into the stem cells.
Earlier clinical trials involving HIV-related lymphoma patients provided stem cells treated with one type of anti-HIV RNA. Their stem cells contained the anti-HIV gene for a short time, but after a few months the cells died off, presumably because the genetically treated stem cells were unable to replicate. But researchers hope new advances will allow the body to keep producing HIV-resistant white blood cells, Zaia said.
The new trial also will mark the first time that scientists will use three different anti-HIV segments at one time, which they hope will prevent HIV from developing resistance. “The virus can mutate around any one element, but it’s hard to mutate around three things,” he said.
The method has already shown promise in pre-clinical animal studies conducted by City of Hope researchers working with Ramesh Akkina, Ph.D., of Colorado State University, and colleagues.
“This could provide the optimal chance of knocking down the virus long-term for patients with high-risk AIDS-related lymphomas,” Zaia said. The method cannot completely rid the body of every trace of HIV, however, since the virus is harbored in lymph nodes and other parts of the body, he said.
The pilot study also included these City of Hope researchers: principal investigator Amrita Krishnan, M.D., associate professor and physician in the Division of Hematology & Hematopoietic Cell Transplantation (HCT); Stephen Forman, M.D., the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and chair of the Division of Hematology & HCT; Jiing-Kuan Yee, Ph.D. professor in the Division of Virology; and John Rossi, Ph.D., chair and professor in the Division of Molecular Biology.