• Biodegradable gel boosts immune system's

    From ScienceDaily@1:317/3 to All on Wednesday, April 06, 2022 22:30:40
    Biodegradable gel boosts immune system's attack on several cancers in
    mice

    Date:
    April 6, 2022
    Source:
    University of Wisconsin-Madison
    Summary:
    The gel, tested in mice, releases drugs and special antibodies that
    simultaneously deplete immune-blocking cells called macrophages from
    the surgical site and activate T cells so they can attack cancer.



    FULL STORY ==========================================================================
    A new biodegradable gel improves the immune system's ability to keep
    cancer at bay after tumors are surgically removed.


    ==========================================================================
    The gel, tested in mice, releases drugs and special antibodies that simultaneously deplete immune-blocking cells called macrophages from
    the surgical site and activate T cells so they can attack cancer.

    University of Wisconsin-Madison scientists tested the gel on mouse models
    of several cancers. They found that the gel effectively kept in check
    tumors that are known to respond well to this kind of immune therapy,
    like CT26 colon cancers. But the gel also worked well against B16F10
    melanomas, S180 sarcomas and 4T1 triple negative breast cancers, which
    are less responsive to immune therapy and more prone to metastasizing.

    These proof-of-concept experiments will support additional research on
    other animal models that could lead to future clinical trials in people.

    The experiments were led by the lab of Quanyin Hu, a professor in the
    UW- Madison School of Pharmacy, with support from pharmacy professor
    Seungpyo Hong and colleagues in the UW School of Medicine and Public
    Health. The team published their findings April 6 in the journal Nature Communications.

    "We are really glad to see that this local strategy can work against so
    many different kinds of tumors, especially these non-immunogenic tumors,"
    says Hu.

    "We are even more glad to see this local treatment can inhibit tumor metastasis." Surgery is an excellent treatment for many tumors, but
    small numbers of cancer cells that remain after the operation can allow
    tumors to grow back. To counteract this process, the researchers developed their gel to slowly release into the surgical site two key components.



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    One is the drug Pexidartinib, which is approved for use to inhibit the
    function of tumor-associated macrophages. These cells promote the growth
    of tumors, and inhibiting the cells slows that cancerous growth.

    The second component of the gel were platelets -- the bits of cells that
    clot blood -- bound to immune-stimulating antibodies. These antibodies,
    known as anti-PD-1, help the immune system's T cells recognize and attack cancerous cells.

    The researchers hoped that the local release of the antibody-bound
    platelets and Pexidartinib would both maximize their effect near the tumor
    site and minimize side effects that occur when these therapies are given intravenously and circulate widely in the body. Indeed, mice given the
    gel showed insignificant side effects. Bodies degrade the gel over time.

    Hu's team tested the gel against a broad suite of cancers because these
    tumors vary in how they respond to immune-based therapies like the
    anti-PD-1- conjugated platelets. In each case, the gel significantly
    slowed the growth of lingering cancer cells and increased the lifespan
    of mice. The gel also greatly reduced the spread of the metastasizing
    breast cancer model the researchers examined.

    In recent years, Hong and Hu have independently been developing new
    ways to control cancers without traditional chemotherapy, which has
    severe side effects. Now collaborating, they plan to continue testing
    creative approaches that could find their way into human patients in
    the coming years.

    "This is just the initial phase of collaboration between our two labs,"
    says Hong.


    ========================================================================== Story Source: Materials provided
    by University_of_Wisconsin-Madison. Original written by Eric
    Hamilton. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Zhaoting Li, Yingyue Ding, Jun Liu, Jianxin Wang, Fanyi Mo,
    Yixin Wang,
    Ting-Jing Chen-Mayfield, Paul M. Sondel, Seungpyo Hong, Quanyin Hu.

    Depletion of tumor associated macrophages enhances local and
    systemic platelet-mediated anti-PD-1 delivery for post-surgery
    tumor recurrence treatment. Nature Communications, 2022; 13 (1)
    DOI: 10.1038/s41467-022- 29388-0 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220406101701.htm

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