CAR-T defeated HIV
A new study published in the journal Nature Medicine led by James Riley, professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania and Todd Allen, professor of medicine at Harvard University Medical School, describes a new immunotherapy with double CAR T cells that helps in the fight against HIV infection.
The study shows how relatively simple changes in the way T cells are constructed can lead to significant changes in their effectiveness and durability. The development is important for the use of artificially created T cells to fight HIV and cancer.
The global HIV epidemic affects more than 35 million people worldwide. Antiretroviral therapy (ART) is a treatment that can control, but not treat, HIV infection. Patients are forced to take ART daily according to the regime throughout their lives. The main obstacle to the cure of HIV is the viral reservoir – copies of the virus stored in the genome of infected cells. If you stop taking ART, the virus is able to quickly create new copies of itself, which ultimately leads to the development of AIDS.
CAR-T cells are a powerful tool that is currently being used in the treatment of cancer. For therapy, the patient's own T cells are modified to express chimeric antigenic receptors (CAR). These CARS reprogram T cells to recognize and destroy specific atypical or infected cells, such as cancer or HIV-infected cells.
Allen and Riley's research teams worked together to create new HIV-specific CAR T cells that could target and quickly destroy HIV-infected cells, survive and reproduce once in the body and resist infection by HIV itself, since the main target of HIV are the same T cells.
Using a step-by-step approach to solving each problem as it arises, the researchers developed protected double CAR T cells that were able to provide a powerful and long-lasting response against HIV infection while being resistant to the virus itself.
The double CAR T-cell was created by converting two cars into one. Each CAR contained a CD4 protein that allowed targeting HIV-infected cells, and a costimulating domain that signaled the CAR T cell to enhance its immune functions. The first CAR contained a 4-1BB costimulating domain that stimulates cell proliferation and resistance, and the second contained a CD28 costimulating domain that increases the ability to kill infected cells.
Since HIV often infects T cells, the scientists also added the protein C34-CXCR4, which prevents HIV from attaching to the cell and subsequently infecting it. The resulting CAR T cell was long-lived, replicated in response to HIV infection, effectively killed infected cells and was partially resistant to HIV infection.
When protected double CAR T cells were injected into HIV-infected mice, slower HIV replication and fewer HIV-infected cells were observed than in untreated animals. The group also noted a decrease in the amount of the virus and the preservation of CD4+ T cells, the target of HIV in the blood of these animals. In addition, the combination of double CAR T-cell immunotherapy with ART in HIV-infected mice resulted in faster suppression and a smaller reservoir of the virus than in mice treated with ART alone.
The ability of protected double CAR T cells to reduce the viral load of HIV in various tissues and cell types, including CD4+ T cells, makes immunotherapy a potential new tool for the functional cure of HIV.
Article by C.R.Maldini et al. Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo is published in the journal Nature Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Massachusetts General Hospital: Novel dual CAR T cell immunotherapy holds promise for targeting the HIV reservoir.