ILLUSTRATION: RANDY LYHUS
Delivering a one-two punch
That is when City of Hope researchers step in.
Scientists at the institution are investigating a method to fight HIV, the virus that causes AIDS, with genetically modified stem cells. But that is not all. At the same time it seeks to knock down virus levels, the technique aims to eradicate the lymphoma that arises in many HIV-positive patients.
The treatment would be the first to use specially engineered, HIV-fighting genes that are inserted into patients’ own harvested 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 Division 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.”
Scientists presented the research at the 48th annual meeting of the American Society of Hematology in Orlando, Fla., late last year. Zaia now is awaiting approval for an upcoming trial at City of Hope that would incorporate the anti-HIV therapy.
Researchers at City of Hope and other institutions have shown that autologous stem cell transplants can benefit HIV-positive patients with lymphoma. 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 reinfusing the cells into the patient after cancerous cells have been destroyed. Today, autologous stem cell transplants are standard therapy for lymphoma that cannot be cured by regular-dose chemotherapy alone.
In this form of transplantation, the new stem cells develop into white blood cells, immune cells that form the body’s line of defense, after they are reinfused into the body. 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. But upon study approval, scientists would take the stem cells of patients with HIV and lymphoma one step further: They would insert HIV-fighting genetic material into the cells before reinfusing them into the body. Scientists use a lentivirus to carry the gene segments into the stem cells.
Earlier clinical trials involving HIV-related lymphoma patients provided stem cells treated with one type of HIV-fighting genetic material. Their stem cells contained the anti-HIV gene for a short time, but after keep producing HIV-resistant white blood cells, Zaia said.
The new trial would 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.
ALICIA DI RADOJohn Zaia and Amrita Krishnan
The method has already shown promise in preclinical 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 lies deep 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 J. 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 in the Division of Molecular Biology.