Can Modified T Cells Reduce HIV Patients' Long-Term Reliance On ART?
With the discovery that stem cells enable a sustained immune response to HIV, scientists are hoping to eventually reduce patients’ long-term reliance on ART.
Although antiretroviral therapy (ART) has been a literal lifesaver for many individuals with HIV, it does have limitations: It suppresses the virus but doesn’t actually destroy it, and if ART is halted, viral levels rise rapidly. Not only that, ART carries with it the risk of significant side effects.
Researchers have been using hematopoietic stem progenitor cells (HSPCs) to battle cancer and other diseases, and interest is growing in doing the same for individuals living with HIV. Studies indicate that this technique may be a viable option to fight HIV infection, but there are concerns that stem cells might not bestow extended immunity. HIV cells often proliferate in various sites in the body—such as the gastrointestinal tract and the lymph system—for months and years; an effective treatment would have to be able to ferret out these widely dispersed cells and fight them for a potentially long period of time.
A team of researchers at the University of California, Los Angeles and the Fred Hutchinson Cancer Research Center in Seattle set out to learn whether altering HSPCs would enable them to generate a sustained battle against HIV cells. To this end, the team transplanted 2 young male pigtail macaque monkeys with HSPCs that had been engineered with a chimeric antigen receptor (CAR) to target SHIV (simian/human immunodeficiency virus)—a hybrid virus used to study HIV infection in monkeys—and compared the results with those of 2 control macaques who were given nonfunctional CAR receptor cells. The macaques with functional CAR cells were able to continue generating cells for more than 2 years; these cells were able to attack HIV cells in the gastrointestinal and lymph systems without causing any negative side effects.
What makes this study significant, according to the authors, is that they were able to generate CAR cells from HSPCs, thus ensuring that the cells would continue to produce over a long period of time and bestow continued functional immunity against HIV. In contrast, when CAR-modified mature T cells are transferred into a host instead of generated in vivo, there’s a higher risk of “immune exhaustion, limited trafficking to tissues, and lack of functionality at these sites,” the authors wrote. They also noted that the CAR-expressing cells were able to expand and respond appropriately when viral loads rose in the study subjects, as might happen in humans if ART is halted or interrupted.
“An important aspect to eradicating the virus or getting it out of the body is an effective immune response against HIV,” Scott Kitchen, PhD, associate professor of medicine in the division of hematology/oncology at the University of California, Los Angeles and an author of the study, told Contagion ®. While the immune response is crucial in destroying other viruses, it’s traditionally been ineffective against HIV. By treating the study subjects with HSPCs modified with fully functioning CAR molecules, he said, “we’re providing the immune response with a tool.”
The scientists’ goal is to continue testing, hopefully on humans within 2 to 3 years. “We’re currently trying to optimize the stem cell transplantation procedures that are involved,” Dr. Kitchen said, adding that a goal is to wean HIV-positive individuals off of ART, or at least do strategic therapeutic interruptions, in which they go off the medication for periods and then resume taking it. “Eventually, we would like to lessen peoples’ dependence on ART over time. What we’re trying to do is supply them with lifelong immunity.” Not only would HIV be targeted, but perhaps other diseases, too. “We think that this really lays the foundation for treating other types of viral infections,” Dr. Kitchen added.
Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.