Biodegradable hydrogel boosts immune system’s attack on several cancers in mice
University of Wisconsin – Madison | 04-06-2022
A new biodegradable hydrogel improves the immune system’s ability to keep cancer at bay after tumors are surgically removed.
The hydrogel, 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 hydrogel on mouse models of several cancers. They found that the hydrogel effectively kept in check tumors that are known to respond well to this kind of immune therapy, like CT26 colon cancers. But the hydrogel 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 metastasis.
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 hydrogel to slowly release into the surgical site two key components.
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 hydrogel 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 hydrogel showed insignificant side effects. Bodies degrade the hydrogel over time.
Hu’s team tested the hydrogel 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 hydrogel significantly slowed the growth of lingering cancer cells and increased the lifespan of mice. The hydrogel 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.
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Materials provided by the University of Wisconsin-Madison. Content may be edited for clarity, style, and length.
