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    Home > Active Ingredient News > Antitumor Therapy > From two weeks to one day, the new bioscaffold can quickly generate CAR-T cells in the body, and the anti-cancer effect is faster, stronger and more durable

    From two weeks to one day, the new bioscaffold can quickly generate CAR-T cells in the body, and the anti-cancer effect is faster, stronger and more durable

    • Last Update: 2022-05-27
    • Source: Internet
    • Author: User
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    Schematic diagram of MASTER (white) In recent years, CAR-T cells have become a star targeted therapy for the treatment of tumors
    .

    Because of its unprecedented success against CD19-expressing B-cell malignancies, related products have been approved by the U.
    S.
    Food and Drug Administration (FDA) starting in 2017 and have inspired hundreds of ongoing clinical trials
    .

    Although CAR-T cell therapy has revolutionary potential in the treatment of human malignancies, the complex process required to produce clinical-grade CAR-T cells and the staggeringly high cost remain major obstacles to the clinical application of this therapy
    .

    Recently, in a study published in "Nature Biotechnology", a research team from the University of North Carolina at Chapel Hill developed a bio-guided implantable scaffold for rapid in vivo generation and release of CAR-T cells.

    .

    In a proof-of-concept study of mouse lymphomas, the implantable scaffolds attacked tumors more rapidly than traditional CAR-T cell therapy and translated into stronger and longer-lasting cancer-fighting capabilities
    .

    As we all know, T cells are part of the immune system whose task is to recognize and destroy cells in the body that are infected by invading pathogens; CAR-T cells are T cells engineered to recognize cancer cells and destroy them
    .

    However, its biggest disadvantage is that the price is very expensive, each of which is more than one million yuan
    .

    Because of the high cost, many patients are forced to give up
    .

    A major reason for the high cost is that the cell preparation process is complex and time-consuming, and must be tailored to each cancer patient's circumstances
    .

    Therefore, shortening the time to prepare CAR-T cells is even more critical for patients whose disease is rapidly deteriorating
    .

    In the new study, the researchers sought to address challenges related to the time and cost of CAR-T cell preparation
    .

    To this end, they developed a biotechnology called Multifunctional Alginate Scaffolds (MASTER) for T cell manufacture and release
    .

    MASTER is a biocompatible sponge-like material that looks and feels like a mini marshmallow
    .

    To understand how MASTER works, let's first understand how CAR-T cells are made: First, clinicians collect peripheral venous blood from a patient to extract T cells and ship them to a regulated laboratory
    .

    The researchers "activated" the T cells with antibodies in preparation for reprogramming over several days
    .

    Once the T cells are activated and the virus is introduced into the CAR gene, the researchers reprogram the T cells into CAR-T cells that target cancer cells
    .

    Then, these CAR-T cells are further expanded to the number for clinical treatment
    .

    The entire process takes at least two weeks
    .

    Finally, the CAR-T cells are brought back to the hospital and infused back into the patient
    .

    According to the researchers, MASTER technology takes the tedious and time-consuming steps of activation, reprogramming and amplification all in the patient's body, reducing a process that took several weeks to less than 24 hours
    .

    To start the treatment, the researchers isolated T cells from patients and mixed these unactivated naive T cells with the engineered virus
    .

    The mixture is poured into MASTER, which absorbs it.
    The large pores and spongy properties of the bioscaffold make the virus and cells tightly bound together, which is conducive to the genetic recombination of cells
    .

    Antibodies that activate T cells are also modified on MASTER, so that the cell activation process begins almost immediately
    .

    After implantation, the cell activation process continued, and they began to respond to modified viruses that reprogrammed them into CAR-T cells
    .

    MASTER also contains cytokines that promote cell proliferation
    .

    After implantation, these factors begin to exude to promote the rapid proliferation of CAR-T cells
    .

    Designing the material to dry and absorb the combination of T cells and virus is a crucial step, the researchers said
    .

    Because, wet MASTER does not work
    .

    In the study, the researchers conducted experiments on mice with lymphoma
    .

    One group was implanted with CAR-T cells produced and delivered by MASTER; the other group was treated with conventionally prepared CAR-T cells
    .

    The two groups were compared to a control group that received non-engineered T cells
    .

    The treatment results showed that the MASTER treatment group performed very well
    .

    It takes at least two weeks to prepare CAR-T cells for clinical use from naive T cells; MASTER can be introduced into mice within hours of isolating naive T cells
    .

    The researchers found that because the cells were engrafted within hours of isolation, this minimal manipulation created healthier cells that exhibited fewer markers associated with poorer cancer-fighting efficacy of CAR-T cells
    .

    Specifically, the MASTER technology results in cells that are less differentiated, which translates to stronger and longer-lasting cancer-fighting capabilities
    .

    In addition, these cells also displayed fewer markers of T cell exhaustion
    .

    The end result was that mice treated with CAR-T cells through MASTER were significantly better at fighting tumors than mice treated with conventional CAR-T cells
    .

    The improvement in the anticancer effect was more pronounced over a longer period of time when the mice faced lymphoma recurrence
    .

    The team says MASTER technology is very promising in liquid tumors, such as lymphomas, but they are particularly eager to see the effects of MASTER on solid tumors, including pancreatic and brain tumors
    .

    Currently, the team is working with industry partners to commercialize the technology
    .

    But the researchers say there is still a lot of work to be done before it can enter clinical applications
    .

    If MASTER is eventually approved for clinical use, how much will it cost? The researchers are optimistic that it will be significantly lower than existing CAR-T cell products
    .

    "We are also exploring opportunities with other industry partners to apply the fundamental concepts of MASTER to regenerative medicine and autoimmune diseases," said Yevgeny Brudno, Ph.
    Treatment
    .

    ” Paper link: https://
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