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.


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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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