HIV is a hidden virus that can be stored in infected cells and re-emerge if treatment is stopped. Now, a team of researchers has found a way to narrow the virus pool by adjusting a cancer immunotherapy technique to boost immune cells in mice.
Although HIV is still a deadly disease, it can be controlled through antiretroviral therapy (ART). The treatment requires daily medication to suppress the virus, which is not yet fully removed from the body. This is because copies of the virus can be hidden in the genomes of infected cells, and if antiretroviral therapy is interrupted, the virus will re-emerge.
Addressing this viral library may be key to a cure, with recently gratifying results for CRISPR-Cas9, a drug and gene-editing tool known as HDAC inhibitors. Now, a team of scientists has adapted a cancer immunotherapy treatment to eradicate the virus.
Chimed antigen receptor T-cell immunotherapy (CAR-T) involves removing immune cells from a patient, reprogramming them to specific disease-specific (usually cancer)-specific cells, and then reintroducing them into the body. In the new study, the team created a new type of T-cell for HIV. This involves engineering T-cells to express two different types of CAR –receptors that bind to the target. Each CAR has a CD4 protein that targets HIV, and one of two “co-stimulation domains” to improve its functionality. One helps stimulate the proliferation and persistence of T cells, while the second helps it kill infected cells more effectively. The final ingredient is a protein called C34-CXCR4, which prevents HIV infection from being modified by the T-cells themselves.
The end result is that CAR-T cells can effectively kill infected cells, replicate and survive long-term in the body, and at least partially resistant to HIV infection. In tests on infected mice, the team found that dual CAR-T cell therapy made HIV replication slower and infected fewer cells than in untreated mice. In the blood of mice treated, the researchers also found a decrease in the number of viruses, while HIV typically attacks CD4-T cells that survive more. When combined with traditional ART, the virus was suppressed faster and the virus library shrunk, compared to mice that received ART alone.
“These protected dual CAR-T cell therapies reduce the burden of HIV in a variety of tissue and cell types, including long-lived memory CD4-T cells, and we believe in supporting CAR T cell therapy as a new tool for achieving functional cures for HIV,” said Todd Allen, co-lead researcher on the study.
The team says the breakthrough could not only lead to new treatments for HIV, but also improve the use of CAR-T cells for cancer. Of course, this work is still at a very early stage, so there is no guarantee that the results will continue to be in humans.
The study was published in the journal Nature Medicine.