Gene Therapy Using CAR-T could Interfere With the Ability of HIV to Infect Cells
Antiviral drugs can suppress the amount of HIV in the body to nearly undetectable levels, but only an effective immune response can eradicate the virus. Therefore, researchers have been seeking a way to improve the body’s ability to combat the virus by engineering blood-forming stem cells to specifically target and kill HIV-infected cells for the life of the individual.
Although chimeric antigen receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer – and show promise in treating HIV-1 infection – the therapy may not impart long-lasting immunity. Attributable to which we need T cell-based products that can respond to malignant or infected cells that may reappear months or years after treatment.
In this direction, scientists at UCLA are now engineering blood-forming stem cells that can carry a CAR to cells.
The researchers used a CAR molecule that hijacks the essential interaction between HIV and the cell surface molecule CD4 to make stem cell-derived T-cells target infected cells. When the CD4 on the CAR molecule binds to HIV, other regions of the CAR molecule signal the cell to become activated and kill
the HIV infected cell.
Further, when tested in animals, the blood-forming stem cells that were modified with the engineered CAR entered the bone marrow and matured into functional, circulating immune cells. If it works in people, it could be most effective when used in conjunction with antiretroviral drugs, possibly even eradicating HIV reservoirs—hidden stores of the virus that otherwise wouldn’t respond to treatment, the researchers suggest.
These findings are the first to show that blood-forming stem cells can be modified with a CAR therapy that can safely engraft in the bone marrow, mature and become functional immune cells throughout the body.
And the team hopes that this could lead to the development of an approach allowing for safe, lifelong immunity to HIV, reducing dependence on antiviral medications, lower the cost of therapy, and permit the possible eradication of HIV from its hiding places in the body.
