NIH awards grant to UCLA to develop CAR T-cell therapies for HIV
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The NIH awarded a $13.65 million grant to researchers at University of California, Los Angeles, to develop chimeric antigen receptor T-cell therapies for the treatment of HIV.
The 5-year grant will fund a collaboration of UCLA, biotechnology company CSL Behring, and University of Washington and Fred Hutchinson Cancer Research Center.
The collaboration will be led at UCLA by Scott Kitchen, PhD, associate professor of medicine and director of the Humanized Mouse Core Laboratory at David Geffen School of Medicine, and Irvin S.Y. Chen, PhD, director of UCLA AIDS Institute at David Geffen School of Medicine. Both Kitchen and Chen have conducted previous research on using CAR T cells to treat HIV.
HIV, like many cancers, is a chronic disease state, Kitchen said.
“A robust immune response is required to clear out any type of viral infection,” he told Healio. “This is especially true for HIV, which requires both a robust and prolonged response to clear the virus.”
Kitchen cited two patients who are still in remission for HIV after undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies, the most recent of whom is commonly referred to as the London patient.
“They were transplanted with cells that were protected from HIV infection and, when their immune systems reconstituted, the process cleared the virus,” Kitchen said.
The cells reacted against the HIV to eradicate the virus and they were protected from becoming newly infected because the cells came from donors who had a natural mutation that provided resistance to HIV infection.
“Our CAR T-cell approach is different from that which is being applied in the cancer space,” Kitchen said.
His team’s research involves programing the immune system at the stem cell level so that when the cells engraft in the treated patient, it allows them to produce HIV-specific T cells within the body.
“Using the stem cell approach also allows the patient to produce these cells for the rest of their lifetime,” he added.
Kitchen summarized the approach as a combination of three strategies: engineering cells at a stem-cell level to produce CAR T cells; producing stem cells that are engineered to be protected from infection; and engineering cells to produce neutralizing antibodies that target HIV infection within the patient’s body.
Unlike the allogeneic HSCT method used for the London patient, Kitchen said his group will use an autologous approach. The cells for this research will be drawn from the patient, modified and reinfused in the patient. The modified CAR T cells will target HIV and protect the CAR molecules from becoming newly infected.
The plan is to combine the CAR T cells with antiretroviral therapy.
The investigational treatment would be a one-time infusion, Kitchen said.
“Once these cells are given to the individual and they engraft, we anticipate that they will produce antiviral effects for the life of the patient,” he added.
National Institute of Allergy and Infectious Diseases is the primary funder of the grant, which was awarded based on preclinical findings. The grant will enable the team at UCLA and their collaborators to start the next phase of research, merging the three strategies into a single approach for potential clinical applications.
“It enables us to combine multiple successes we have had into a unified approach to try to cure HIV infection,” Kitchen told Healio.
The strategy has the potential to be curative when combined with other approaches, such as antiretroviral therapy, he said.
“We are looking at this as a way to provide the immune system with tools to overcome its defects in clearing HIV infection from the body,” Kitchen said. “The ultimate goal is to allow people to end their lifelong dependence on antiretroviral therapy.”
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