Source: University of California, Los Angeles
Summary: Researchers through gene therapy, engineered blood-forming stem cells to carry chimeric antigen receptor (CAR) genes to make cells that can detect and destroy HIV-infected cells.
Antiviral drugs can suppress the amount of HIV (Human Immunodeficiency Virus) in the body to almost undetectable levels, but only an effective immune response is crucial for the control of viremia and the elimination of HIV infected cells. Previous research has been seeking a way to improve the body’s ability to combat the virus by specifically targeting and killing 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, however, significant limitations are persistent and the therapy may not impart long-lasting immunity.
Researchers from the University of California, Los Angeles, through gene therapy, engineered blood-forming stem cells (hematopoietic stem/progenitor cells – HSPCs) to carry chimeric antigen receptor (CAR) genes to make cells that can detect and destroy HIV-infected cells. These engineered cells not only destroyed the infected cells, they persisted for more than 2 years without any adverse effects, suggesting the potential to create long-term immunity from the virus that causes AIDS (Acquired Immunodeficiency Syndrome). Such an approach is likely to work best when performed in combination with other treatment strategies, such as antiretroviral therapy. The study findings were published in the journal PLOS Pathogens.
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. These findings are the first to show that HSPCs can be modified with a CAR therapy that can safely engraft in the bone marrow, mature and become functional immune cells throughout the body. Researchers hope that this type of therapy could reduce infected individuals’ dependence on antiviral medications, lower the cost of therapy, and permit the possible HIV eradication from its hiding places in the body.
More Information: Anjie Zhen et al, “Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS”, PLOS Pathogens (2017).