By Casey Ostheimer, WNPRC editorial intern
March 30, 2022
The majority of replicating HIV – and its monkey version, simian immunodeficiency virus (SIV) – is found in follicles of the lymphoid tissues; however, most cytotoxic T-lymphocytes, which are the cells that can clear HIV from the body, are not able to reach the follicles. This explains the need for lifelong use of the current standard treatment, antiretroviral therapy. 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 life-long 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 that targets 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 that expressed a chimeric antigen receptor (CAR) targeting the SIV virus. They added a follicular homing receptor called CXCR5 with the idea that 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 that these T-cells could replicate and proliferate 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 that were not given the CAR/CXCR5 T-cell immunotherapy. The researchers and veterinarians also looked at possible side effects of this treatment and found that 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 an effective and safe treatment of engineered T-cells for HIV infection. Data from these researchers sets 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.