What’s the Role of Natural Killer Cells in Curing HIV?

Research question
Last month this update discussed a study of “elite controllers,” people living with HIV (PLWH) who are able to maintain undetectable levels of virus in the absence of antiretroviral therapy (ART).

Conducted by two amfAR-funded scientists, Drs. Mathias Lichterfeld and Xu Yu, the study found high levels of natural killer (NK) cells—cells capable of targeting HIV-infected cells—in these controllers, along with high levels of the immune hormone IL-15. IL-15 can enhance the killer function of NK cells and prolonged their survival. Whether this observation could be translated into an effective treatment and potential cure for the vast majority of PLWH who are not elite controllers was unknown.

Findings
Dr. Timothy Schacker and colleagues at the University of Minnesota conducted a pilot, phase 1 study of a single injection of NK cells into six PLWH, all males aged 34 to 56 who had been on effective ART for 2-17 years. The NK cells were donated by relatives of the study subjects and selected for being at least “haploidentical,” i.e., sharing at least half of their tissue types and thus unlikely to be rejected by the immune system.

Four subjects also received N-803, a “super-IL-15” with 25 times greater activity than its parent protein, and two received IL-2, another immune hormone capable of enhancing NK activity. The infused NK cells persisted for at least six to eight days and, in one of the six subjects, were still present 28 days after their administration. In four of the six individuals, biopsies of lymph nodes, rectum, and other intestinal tissue were obtained before and after cell and immune hormone treatment. Numbers of HIV-infected cells decreased in all tissues sampled.

Impact
The authors concluded that their data “suggested that providing functional NK cells could be a potential part of a successful strategy to cure HIV. Although it is not practical to consider infusions of haploidentical NK cells on a scale that would benefit the millions of PLWH worldwide, this approach does provide proof of principle.”

amfAR’s role
amfAR was a funder of this research.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/38207119

Dr. Laurence is amfAR’s senior scientific consultant.