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On August 31st Nature Medicine published a new study by research institutions such as Harvard Medical School, the Ragon Institute, and the Perelman School of Medicine at the University of Pennsylvania, which presents a new dual-specific CAR-T cell immunotherapy.
This engineered CAR-T cell can reduce hiv-infected viralemia, has the characteristics of strong proliferation, resistance to T-cell depletion, and in combination with antiretroviral therapy can accelerate the suppression of HIV, reduce the viral burden of tissue.
Jim Riley, co-author of the paper, said: "A relatively simple change in the way engineered T cells can lead to dramatic changes in T-cell efficacy and durability.
is important for using engineered T-cells to fight HIV infection and cancer.
" Source: Nature Medicine More than 35 million people worldwide are infected with HIV.
today, antiretroviral therapy (ART) is a very effective treatment, but it can only control, not cure, AIDS.
obstacle to the cure of AIDS is the HIV virus library, HIV infection in the human body after about 4-6 weeks, you can complete the establishment of the virus library.
virus library is hidden in the genomes of infected cells, with copies of HIV genes.
if antiretroviral treatment is interrupted, HIV can quickly replicate new copies, eventually leading to the development of AIDS.
addition, access to drugs and lifetime adherence to daily medication are also a major barrier for many people living with HIV.
, researchers have been exploring a functional cure for AIDS.
the study, the team worked together to design a new HIV-specific CAR-T cell that contains two CARS and expresses both 4-1BB/CD3-ζ and CD28/CD3-ζ inner domains.
each CAR has a CD4 protein that targets HIV-infected cells and a co-stimulation domain that enhances the immune function of CAR-T cells.
the 4-1BB costulation domain contained in the first CAR stimulates cell proliferation and persistence, and the CD28 costulation domain contained in the second CAR enhances the ability to kill infected cells.
addition, the researchers added C34-CXCR4 to T cells, a protein that prevents HIV from attaching to infected T cells.
resulting long-acting CAR-T cells can respond to HIV infection, effectively killing infected cells, and are partially resistant to HIV infection.
C34-CXCR4 and its protective effect on CD4-CAR-T cells (Source: Nature Medicine) In treating HIV-infected mice with this dual-specific CAR-T cell, the team found that infected mice were treated with bisso-specific CAR-T cells with slower HIV replication and fewer HIV-infected cells than untreated mice.
and treatment reduced the number of viruses in the blood of mice, and CD4-T cells (the preferred target cell for HIV) were preserved.
In addition, when researchers combined dual-specific CAR-T cells with antiretroviral therapy in HIV-infected mice, the virus was suppressed more quickly, and the virus bank was smaller than in mice treated with antiretroviral therapy alone.
The control of HIV replication by dual-specific CAR-T cells (Source: Nature Medicine) "We believe this study supports the use of CAR-T cell therapy as a new tool to target HIV reservoirs for functional cures of HIV.
," said Todd Allen, a professor at Harvard Medical School and author of the paper.
: 1 s Davenport, M. P. et al. Functional cure of HIV: the scale of the challenge. Nature Reviews Immunology (2018) 2 s Maldini, C.R. et al. Dual CD4-based CAR T cells with distinct costimulatory domains domains domains domainsson hiv pathogenesis in vivo. Nature Medicine (2020) 3 s Novel Dual CAR T cell immunotherapy holds for targeting the HIV reservoir (Source: MedicalXpress)