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    Home > Active Ingredient News > Antitumor Therapy > 2021 EBMT | CAR.CD123-NK cells are expected to bring new treatment strategies for CD123-positive children with AML

    2021 EBMT | CAR.CD123-NK cells are expected to bring new treatment strategies for CD123-positive children with AML

    • Last Update: 2021-03-21
    • Source: Internet
    • Author: User
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    Acute myeloid leukemia (AML) is a malignant tumor that threatens the lives of children.
    The current survival rate of children with AML is about 70%.

    For children with high-risk AML, allogeneic hematopoietic stem cell transplantation after intensive chemotherapy is the standard treatment.

    Although this treatment can improve the prognosis of children, 25%-30% of children will have disease recurrence, leading to treatment failure.

    Although the current CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has achieved great success in malignant B-cell lymphoma, the preparation of CAR-T cells is relatively expensive and time-consuming.

    In contrast, CAR cells based on natural killer (NK) cells have the advantages of low allogeneic reactivity and high cytotoxicity to tumor targets.

     The high expression of CD123 in AML leukemia stem cells is a potential new target for CAR cell therapy.

    The Italian research team explored the anti-tumor activity of CAR.
    CD123-NK cells in vivo and in vitro.

    The results of the study will be announced at the 47th Annual Meeting of the European Association of Blood and Bone Marrow Transplantation (EBMT 2021) in 2021.

    The editor organizes the main content as follows for the reference of readers.

    01 Research method: The study uses retrovirus as a vector to modify CAR.
    CD123 cells and 4.
    1bb as a costimulatory domain.
    NK cells are generated from the peripheral blood of a healthy donor (HD) and pass through feeder-free FBS in the presence of IL2 Methods Carry out in vitro expansion and evaluate the cellular function of CAR.
    CD123-NK cells in vivo and in vitro.

    02Research results After genetic modification of retroviral vector, NK cells showed stable CAR.
    CD123 expression (58%±21.
    9%) in vitro, and showed significant anti-leukemia activity against CD123-positive tumor cells (Figure A below) ). Compared with untransduced NK cells, CAR.
    CD123-NK cells have higher anti-leukemia activity against CD123-positive primary AML cells collected from children with AML (P=0.
    005) (Figure B below).

    In order to test the targeted off-target effect of this treatment, the study conducted short-term clone formation experiments on CD34-positive bone marrow-derived cells from healthy donors pre-cultured with unmodified or CAR.
    CD123-modified NK cells.
    No BFU- Significant reduction of E clones and CFU-GM clones.

    The study also established a xenograft immunodeficiency mouse model of humanized AML CD123-positive THP-1 cell line.

    Studies have shown that two consecutive infusions of CAR.
    CD123-NK cells can significantly improve the overall survival rate (OS) of mice.
    81% of the treated mice survived on the 125th day of treatment (OS of mice receiving unmodified NK cells) Rate is 0%) (as shown in the figure below).

    03 Research conclusions The in vivo and in vitro research data confirmed the feasibility of the feeder-free generation of stably transduced CAR.
    CD123-NK cells.

    Targeting CD123-positive leukemia cells may be a new treatment strategy, which is expected to provide a new treatment method for children with relapsed and refractory AML.

    Reference source: S.
    Caruso, R.
    Ciccone, Z.
    Abbaszadeh, et al.
    EngineeredCAR.
    CD123 NK cells as an innovative "off the shelf" strategy to treatCD123+ childhood acute myeloid leukaemia.
    The 47th Annual Meeting of the EBMT.
    Abstract OS2- 8.
    Poke "read the original text", we will make progress together
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