Engineered immune cells known as chimeric antigen receptor T cells (CAR-T) have grabbed headlines this year for their potential to cure some patients with leukemia and lymphoma. But CAR-T is generating plenty of interest beyond cancer, and scientists at the University of California, Los Angeles are among those investigating whether the approach would work against HIV, too.
Their technique revolves around CD4, a protein on the surface of immune cells that HIV uses to infect cells. The scientists used gene therapy to engineer blood-forming stem cells that can carry a CAR to cells. The CAR they developed binds to HIV via CD4, prompting other parts of the CAR to become activated and kill HIV, according to a statement. The research was published in the journal PLOS Pathogens.
The UCLA team believes a CAR-T approach to treating HIV would help combat one of the major shortcomings of antiretroviral drugs. These treatments often suppress HIV to the point where it is no longer detectable, but they can’t completely clear the virus without a full-on attack from the immune system. An effective CAR-T treatment holds the potential to provide lifelong immunity to the virus, the UCLA researchers believe.
In animal testing, the blood-forming stem cells that were modified with the engineered CAR entered the bone marrow and matured into functional, circulating immune cells. If it works in people, it could be most effective when used in conjunction with antiretroviral drugs, possibly even eradicating HIV reservoirs—hidden stores of the virus that otherwise wouldn’t respond to treatment, the researchers suggest.
Other academic groups are working on CAR-Ts to attack HIV, including the University of Pennsylvania, which was the original developer of Novartis’s Kymriah, the first FDA-approved CAR-T for cancer. In October, the Penn team published research showing their anti-HIV CAR-T prevented the virus from spreading among human cells. And in mice taken off antiretroviral drugs, it suppressed viral levels.
A number of other immune-boosting treatments are under investigation in HIV. They include drugs that inhibit PD-1 and other “checkpoints” that prevent the immune system from eliminating pathogens, as well as antibody-based vaccines and the gene-editing technique CRISPR.