The state stem cell agency, the California Institute for Regenerative Medicine (CIRM), today approved funding a UC Davis Health System research team to conduct a clinical trial using bioengineered stem cells to treat HIV patients suffering from lymphoma, one of the deadly conditions associated with the disease.
The $8.5 million grant will be used to test gene-modified hematopoietic (or blood-forming) stem cells in patients and then monitor and analyze their effectiveness on the human immunodeficiency virus (HIV).
The UC Davis team, led by Mehrdad Abedi and Joseph Anderson, developed a gene therapy strategy that in animal models showed promise as a functional cure for HIV, the virus that causes AIDS. That achievement, which involved improving a technique for purifying populations of HIV-resistant stem cells, opened the door for the human clinical trial funded by today’s CIRM grant. The researchers anticipate launching their study with patients in the coming year.
“We’re hoping this new hematopoietic stem cell gene therapy for HIV will provide a one-time treatment, with the possibility of controlling both the lymphoma as well as HIV itself by eliminating the reservoirs of HIV in patients responsible for persistence of the disease,” said Mehrdad Abedi, an associate professor of internal medicine, a stem cell transplant specialist at the UC Davis Comprehensive Cancer Center and the principal investigator for the new CIRM grant.
HIV remains a major health problem, with millions of people infected worldwide and causing enormous health burdens on individuals and society. Individuals with HIV, who have weaker immune systems, are at higher risk for lymphoma, which begins in immune system cells. While antiretroviral therapies have dramatically helped treat HIV, a growing number of patients develop highly resistant forms of the virus as well drug toxicity from medications and chronic illnesses such as cancer. Mounting evidence also suggests that these conditions occur more often and at a younger age in HIV patients than in uninfected people, and may increase the risk of malignancies.
“We will be targeting HIV-related lymphoma patients who require a transplant as a part of their standard of care,” said Abedi. “This provides us with an ideal setting to test the safety and efficacy of our bioengineered stem cells. Once the specially engineered stem cells are transplanted, new HIV-resistant immune cells will be produced. We’ll replace the patient’s immune system with HIV resistant cells, depleting the viral load associated with the disease without requiring conventional antiretroviral therapies.”
Today’s grant award to UC Davis is part of several CIRM funding opportunities specifically designed to accelerate the completion of stem-cell based therapies. The agency plans to devote significant internal resources to help actively advance the project.
“The decision to invest in this therapy is just one part of the work we do to try and help projects like this succeed,” says C. Randal Mills, Ph.D., president and CEO of CIRM. “Our mission is to accelerate the development of therapies for patients with unmet medical needs, and money is an important part of that, but so is the support we provide by assigning each clinical program a Clinical Advisory Panel. These advisory panels consist of subject matter experts, CIRM science officers and a patient advocate who will work with the researchers, guiding and advising them and doing all they can to help them succeed.”
In their recommendation to CIRM’s governing board, grant reviewers called the UC Davis project one of “exceptional merit.” The upcoming study has the potential to provide patient care benefits beyond just for those who participate in the clinical trial.
“While we’re planning to first test our therapy in patients with lymphomas, our ultimate goal is to expand this treatment to all HIV patients” said Anderson, co-principal investigator on the grant and a researcher at the UC Davis Institute for Regenerative Cures who developed the improved viral vector used to insert genes that provide HIV resistance.
“Our vector contains a gene that tags the surface of the HIV-resistant stem cells, which enables us to ensure that only the ones resistant to HIV infection are transplanted. If we can prove effectiveness in our upcoming clinical trial, this new approach could benefit a large number of HIV positive patients, both with and without HIV-related malignancies,” added Anderson.
Anderson and Abedi also point to the potential fiscal benefits of their new treatment approach if the clinical trial proves to be ultimately successful in curing HIV. They anticipate that the one-time cost of therapy using gene-modified stem cells will be far less expensive than the estimated $1.5 million (and rising) cost of lifelong antiretroviral therapy for HIV patients, which is the current standard of care.
Other UC Davis physicians and research scientists working on the new HIV/stem cell study include Theodore Wun, Richard Pollard, David Asmuth, Jan Nolta, Gerhard Bauer, Geralyn Annett, Xiao-Dong Li and Frederick Meyers.