Investigational Gene Therapy Produced 2 Year Immunity Against HIV

In 2017, the FDA approved the very first gene therapy, tisagenlecleucel (Kymriah) for refractory B-cell precursor acute lymphoblastic leukemia, and subsequently approved axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma and Luxturna (voretigene neparvovec-rzyl) for rare vision loss disease.

After these groundbreaking drugs were approved, numerous studies emerged demonstrating the potential benefits of gene therapy for other conditions, including multiple sclerosis, hemophilia, and various cancers.

A new study published by PLOS Pathogens suggests that gene therapy may also benefit patients with HIV, who currently have to take daily antiretroviral therapy (ART) to prevent the disease from progressing to AIDS and associated adverse events.

In the study, the authors engineered hematopoietic stem/progenitor cells to carry chimeric antigen receptor (CAR) genes that produce cells able to detect and eliminate HIV-positive cells, according to the study.

Significantly, these cells were observed to destroy HIV-infected cells and elicited a long-term response. The authors discovered that the effects lasted for more than 2 years, which may suggest the gene therapy can lead to long-term immunity against HIV, according to the study.

Currently ART only achieves a partial suppression of HIV. Although viral levels plummet to become nearly undetectable, dormant infected cells can persist. Researchers have been searching for a novel way to completely obliterate the virus from the body with little success.

The goal of the current study was to develop a novel approach to bolster the body's immune response to HIV by developing blood-forming stem cells that are able to target and kill HIV-positive cells for the lifespan of the patient, according to the authors.

The researchers used the gene therapy to overtake the interaction between the virus and the CD4 molecule to produce stem cell-derived T-cells that target infected cells.

The authors found that when CD4 on the surface of the CAR molecule binds to the virus, the molecule kills HIV-positive cells.

When tested in animal models, the engineered CAR T cells produced an immunity of more than 2 years of stable production of the immune cells without adverse effects, according to the study.

Additionally, the authors noted that the CAR T cells were distributed throughout the lymphoid tissues and gastrointestinal tract, which are known sites for HIV replication and persistence, according to the study.

These results are the first to demonstrate that CAR T cells can engraft in the bone marrow and produce functional immune cells, which could lead to the development of a lifelong HIV immunity treatment, according to the authors.

While CAR T cells have been found to be a forceful cancer immunotherapy, the authors said that it may not elicit long-lasting immunity for patients with HIV. Ideally, the therapy must be able to eliminate infected cells that may reappear after treatment, according to the study.

This approach would likely be the most successful when combined with ART. The authors hope that this strategy would be able to lessen reliance on ART, reduce drug costs, and eradicate dormant HIV-infected cells, the study concluded.