A novel gene therapy that engineers patients' own blood-forming stem cells may ofter long-term protection against HIV, the virus that causes AIDS, U.S. researchers said Thursday.
In test animals, the engineered chimeric antigen receptor (CAR) T cells not only destroyed the infected cells, they persisted for more than two years, according to the study published in the peer-reviewed PLOS Pathogens.
"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," said a press release from the University of California, Los Angeles (UCLA), whose researchers led the study.
"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."
CAR T-cells have emerged as a powerful immunotherapy for various forms of cancer and showed promise in treating HIV-1 infection.
In the new study, researchers modified the treatment to make it able to respond to HIV-infected cells that may reappear months or years after treatment.
Because HIV uses CD4 to infect 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,"the UCLA release said.
The researchers found that, in mice and monkeys, modification of the blood-forming stem cells resulted in more than two years of stable production of CAR-expressing cells without any adverse effects.
In addition, these cells were widely distributed throughout the lymphoid tissues and gastrointestinal tract, which are major anatomic sites for HIV replication and persistence in infected people.
Most important, engineered CAR T-cells showed efficacy in attacking and killing HIV-infected cells.
"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," the UCLA release said.
"This could lead to the development of an approach allowing for safe, lifelong immunity to HIV. Such an approach is likely to work best when performed in combination with other treatment strategies, such as antiretroviral therapy."
It's hoped that this type of therapy could reduce infected individuals' dependence on antiviral medications, lower the cost of therapy, and permit the possible eradication of HIV from its hiding places in the body, the researchers added.
