Human immunodeficiency virus (HIV) attacks the body’s immune system, resulting in rashes, fevers, fatigue, swollen lymph nodes, and other symptoms. It affects over 37 million people globally. When left untreated, HIV infections can progress to acquired immunodeficiency syndrome (AIDS), leading to a damaged immune system, severe opportunistic infections, and death.
Most replicating HIV – and its monkey version, simian immunodeficiency virus (SIV) – is found in follicles of the lymphoid tissues. However, most cytotoxic T-lymphocytes, the cells clearing HIV from the body, cannot reach the follicles. This explains the need for lifelong use of antiretroviral therapy’s current standard treatment. However, only 57% of those living with HIV are undergoing antiretroviral therapy, which leaves the rest able to infect others with the virus. Therefore, there is an urgent need for new treatment options, especially for those who do not have lifelong access to healthcare.
A group of AIDS researchers working with immunology and animal care experts on rhesus monkeys at the Wisconsin National Primate Center investigated the possibility of a new therapy targeting virus-specific T-cells to the follicles. They did so by engineering therapeutic T-cells to enter and concentrate in the lymphoid follicles to reduce viral replication. Led by Pamela Skinner, professor of veterinary and biomedical sciences at the University of Minnesota, the team used T-cells to express a chimeric antigen receptor (CAR) targeting the SIV virus. They added a follicular homing receptor called CXCR5 so the CAR/CXCR5 T-lymphocytes could kill the infected cells in the lymphoid follicles. The homing receptor allowed the T-cells to migrate into the follicles, which previously limited the effectiveness of the body’s response to infection.
In six SIV-infected rhesus monkeys, the CAR/CXCR5 T-cells were able to migrate to the follicles within two days and directly interact with the virally infected cells. Fluorescent imaging allowed the researchers to discover these T-cells could replicate and increase within the follicles. Even though levels of the specialized T-cells declined within four weeks after administration, the treated primates were able to maintain lower concentrations of SIV in their blood and follicles than those not given the CAR/CXCR5 T-cell immunotherapy. The researchers and veterinarians also looked at possible side effects of this treatment and found none of the primates had a poor reaction to T-cell administration.
The study, published in Public Library of Science Pathogens, provided preliminary evidence for effective and safe treatment of engineered T-cells for HIV infection. Data from these researchers set the stage for future preclinical studies involving larger populations of non-human primates to confirm the effectiveness of this treatment, along with studies looking at combining this treatment with other therapies.
