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    Home > Biochemistry News > Biotechnology News > "Science" is heavy!

    "Science" is heavy!

    • Last Update: 2022-01-25
    • Source: Internet
    • Author: User
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    Heart damage or inflammation can cause fibroblasts to overproduce fibrous material, which hardens the heart muscle and impairs heart function.
    This is called cardiac fibrosis
    .

    Cardiac fibrosis can cause many serious diseases, including heart failure, liver disease, kidney failure, and more
    .

    CAR-T cell therapy, the full name is chimeric antigen receptor T cell therapy
    .
    In 2017, the FDA approved the first CAR-T cell therapy for the treatment of leukemia, ushering in a new era of CAR-T cell therapy


    .


    Until now, however, CAR-T cell therapy has required collecting a patient's own T cells and then genetically recombining them in the lab to enable them to recognize specific cancer cells so that they can be identified and removed after infusing them into the body.
    kill
    .

    The whole process is complicated and time-consuming, so the price is very expensive, costing hundreds of thousands of dollars
    .

    CAR-T cell therapies currently on the market are designed to treat blood cancers, but they have also shown promising results in many other types of diseases
    .

    Back in 2019, Jonathan Epstein's team at the Perelman School of Medicine at the University of Pennsylvania demonstrated that CAR-T cell therapy could target overactive cardiac fibroblasts to restore heart function
    .

    However, this CAR-T cell therapy has serious shortcomings in the treatment of myocardial fibrosis-related diseases, because fibroblasts have important functions in the human body, especially in wound healing
    .

    In vitro reprogrammed CAR-T cell therapy, once injected into the human body, can persist in the human body for months or even years, thereby inhibiting fibroblasts for a long time and impairing functions such as wound healing
    .

    On January 6, 2022, researchers at the Perelman School of Medicine at the University of Pennsylvania published a paper in the journal Science, titled: In vivo generation of CAR-T cells to treat heart damage
    .

    The research team developed an in vivo-generated transient engineered CAR-T cell therapy that delivers mRNA by injecting lipid nanoparticles (LNPs) to reprogram T cells to recognize cellular cardiac fibrosis, thereby reducing fibrosis and restoring cardiac function in mice model of heart failure
    .

    This approach is similar to mRNA vaccines
    .
    It only takes a single injection to generate CAR-T cell therapy in the body


    .


    The paper has a strong lineup of authors, including chief scientist Jonathan Epstein of the Perelman School of Medicine at the University of Pennsylvania, Drew Weissman, one of the founders of mRNA technology, and Carl June, the father of CAR-T


    .


    In this new study, the research team designed a novel CAR-T cell therapy based on mRNA technology, using lipid nanoparticles (LNP) for delivery to recode T cell receptors to targeted fibroblasts via mRNA Cell activating protein (FAP), LNP vector has been widely used and validated in 2019-nCoV mRNA vaccine
    .

    The LNP vector recognizes CD5, which is highly expressed by T cells, thereby specifically targeting T cells to generate FAP-CAR-T cells
    .

    Subsequently, the research group conducted treatment experiments on mouse models of cardiac injury
    .

    mRNA was encapsulated with CD5/LNP and injected into mice
    .

    These mRNA molecules successfully entered mouse T cells, effectively reprogramming the T cells, and targeting them to attack activated fibroblasts
    .

    This reprogramming was temporary, and the messenger RNA was not integrated into the T cell genome
    .
    After a few days, these T cells recovered and no longer targeted fibroblasts


    .


    Importantly, in just a few days, the mRNA induced the reprogramming of a large number of CAR-T cells, resulting in a dramatic reduction in myocardial fibrosis in the mice and the return of the heart to normal size and function
    .

    Since mRNA is only stable in the body for a period of time (about a week), the in vivo generation of this engineered CAR-T cell therapy is transient, unlike traditional viral vector-based in vitro reprogrammed CAR-T cell therapy
    .
    Therefore, it does not inhibit fibroblasts in the long term, impairing functions such as wound healing


    .


    Traditional CAR-T cell therapy involves taking a patient's T cells, genetically modifying, reprogramming and expanding them in the lab, and then infusing them into the patient


    The whole process is complicated and tedious, and the cost is high, making this breakthrough treatment method difficult to promote


    The transient engineered CAR-T cell therapy developed in this study generates CAR-T in vivo through LNP delivery of mRNA, which greatly expands the application prospects of CAR-T and mRNA technology


    In addition, the method is more controllable and simpler in the process, which is expected to greatly reduce the cost and price of CAR-T cell therapy


    The team said they will continue to test this mRNA-based transient CAR-T cell therapy, hoping to advance to human clinical trials as soon as possible



     

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