A new paper on AIDS research has been published in the journal Nature Medicine.
team, led by Professor Jim Riley of the Perelman School of Medicine at the University of Pennsylvania and Professor Todd Allen of the Ragon Institute at Harvard University, introduced a new two-specific CAR-T cellular immunotherapy that could help fight HIV infection.
recent years, CAR-T cells have provided powerful tools for treating cancer.
this therapy allows T-cells to identify specific cells and remove them by transforming the patient's own immune T cells to express chimic antigens (CAR).
in addition to targeting cancer cells, designing different CAR can also allow T cells to identify and remove other types of diseased cells.
study, scientists designed a new CAR-T cell that specifically targets HIV-infected cells.
because the main target of HIV infection is T cells, so this CAR-T cell in addition to being able to survive and multiply in the body, it also needs to be able to resist HIV infection.
the Immune T cells (pictured: NIH) that express CD4 from HIV infection, the researchers developed a dual-specific CAR-T cell equipped with two types of CAR on a single cell.
each CAR expresses the extracellular domain of cd4 proteins, enabling it to target HIV-infected cells, and the two CARS contain 4-1BB/CD3-ζ and CD28/CD3-ζ, respectively, which stimulate cell proliferation and persistence, and the latter, which enhances the ability to kill infected cells.
same time, a membrane fusion inhibitor called C34-CXCR4 was added to the CAR-T cell to prevent HIV attachment and protect CAR-T cells from HIV infection.
T cell surface equipped with a schematic of two CAR and membrane fusion inhibitors (Photo source: Reference 1) so that the final researchers produced CAR-T cells can identify hiv-infected cells and effectively kill them, they can also have a certain resistance to HIV infection.
in HIV-infected mice, the researchers tested the effects of the new CAR-T cells.
car-T cells slowed HIV replication and infected fewer cells than the untreated control group.
tests on animal blood showed that the viral burden of CD4-positive T-cells was effectively reduced after treatment, meaning that the most important HIV infection targets were effectively protected.
addition, this dual-specific CAR-T cell, combined with existing antiretroviral (ART) drugs, accelerates viral replication in HIV-infected mice, twice as fast as art alone.
that this suggests that CAR-T cell therapy can reduce the reservoir of viruses formed in animals during ART.
Mice receiving both CAR-T cell and ART therapy were completely inhibited after 2 weeks of treatment, and the art-only control group took 4 weeks (Photo Source: Reference 1) Summary of the research paper concluded that the results "demonstrate that the new dual-specific CAR-T cell products are more effective and have the potential to treat HIV infection effectively".
study used a relatively simple engineering approach to change T-cells, bringing about dramatic changes in efficacy and durability.
, Professor Riley added, "this finding is important for the use of engineered T cells to fight HIV and cancer."
"References. . . . Colby Maldini et al., (2020) Dual CD4-based CAR T cells with distinct costimulatory domains domains of the mayoni HIV pathogenesis in vivo. Nature Medicine. DOI: Novel Dual CAR T cell immunotherapy holds promise for targeting the HIV reservoir. Retrieved Sep. 2, 2020, from