HIV is an insidious virus, able to hibernate inside infected cells ready to re-emerge if treatment is stopped. Now, a team of researchers has found a way to shrink that viral reservoir by adapting a cancer immunotherapy technique to supercharge immune cells in mice.
While HIV is still a deadly disease, it can be brought under control with antiretroviral therapy (ART). This treatment involves taking a daily regimen of drugs that suppress the virus, which currently can’t be completely removed from the body. That’s because copies of the virus can hide way in the genome of infected cells, waiting to emerge again if the ART is interrupted.
Tackling this viral reservoir may be the key to a cure, with promising results recently coming from drugs called HDAC inhibitors and the gene-editing tool CRISPR-Cas9. Now, a team of scientists has tweaked a cancer immunotherapy method to root out this HIV reservoir.
Chimeric Antigen Receptor (CAR) T cell therapy involves removing the immune cells from a patient’s body, reprogramming them to target cells with a specific disease, usually cancer, then reintroducing them to the body.
For the new study, the team created a new type of T cell that targeted HIV. This involved engineering the T cells to express two different types of CARs – the receptors that bind to the target. Each CAR has a CD4 protein that lets it target HIV, and one of two “co-stimulatory domains” that boosts its function. One helps stimulate the T cells’ proliferation and persistence, while the second helps it kill infected cells more effectively. And the final ingredient was a protein called C34-CXCR4, which prevents HIV from infecting the modified T cells themselves.
The end result was CAR T cells that were effective at killing infected cells, could replicate and live for a long time in the body, and were at least partially resistant to infection by HIV.
In tests in infected mice, the team found that the dual CAR T cell therapy caused HIV to replicate slower and infect fewer cells than in untreated mice. In the bloodstreams of treated mice, the researchers also found reduced amounts of the virus and more surviving CD4+ T cells, which HIV usually attacks. When combined with conventional ART, the virus was suppressed even faster and the viral reservoirs shrank, compared to mice that received ART alone.
“The ability of these protected Dual CAR T cells to reduce the HIV burden in a variety of tissues and cell types, including long-lived memory CD4+ T cells, we believe supports the approach of using CAR T cell therapy as a new tool to target the HIV reservoir towards a functional cure for HIV,” says Todd Allen, co-lead researcher on the study.
The team says that the breakthrough could not only lead to a new treatment for HIV, but also improves the use of CAR T cells for cancer. Of course, the work is still in the very early stages, so there’s no guarantee that the results will carry across to humans.
The research was published in the journal Nature Medicine.
Source: Massachusetts General Hospital
