- Researchers have created a drug-releasing hydrogel to reduce the possibility of cancer recurring after surgery.
- They found that the gel could reduce biomarkers of cancer recurrence in mice, specifically those with colon cancer, melanoma, and triple-negative breast cancer.
- However, clinical trials are needed to see whether these results translate over to humans.
Surgery is the first-line treatment for patients with solid tumors. However, often cancer cells can be left behind and, over time, lead to cancer recurring.
Previous research has found that as wounds heal after surgery, immune cells known as tumor-associated macrophages (TAMs) secrete large amounts of anti-inflammatory factors. These factors help remaining tumor cells escape immune surveillance and accelerate their recurrence. Once TAMs were removed cancer, tumor growth was reduced.
Other research has shown that people with fewer TAMs after surgery have reduced tumor growth post-surgery. TAMs have also been frequently used as prognostic markers for cancer recurrence after surgery.
Reducing TAMs and increasing the immune response following surgery could reduce cancer recurrence rates.
Recently, researchers from the University of Wisconsin-Madison, WI, developed a drug-releasing hydrogel that can be applied post-surgery to prevent or slow tumor recurrence.
“The authors hypothesize that the hydrogel delivery system will allow localized delivery of immunotherapy and limit systemic side-effects,” Dr. John A. Thompson, professor of medicine at the University of Washington, who was not involved in the study, told Medical News Today.
“Trials will be needed in cancer patients, but uses of this approach may extend to more cancers than [those they tested],” he added.
The study was published in Nature.
A gradual release mechanism
The researchers included two active compounds in their hydrogel. The first was pexidartinib (PLX), which is known to inhibit TAMs by blocking colony-stimulating factor 1 receptors (CSF1R).
The second was made up of anti-programmed cell death protein 1 (aPD-1) antibodies, which help T cells recognize and attack cancer cells.
They chose to deliver these two compounds via a hydrogel due to its ability to form a “local delivery reservoir” and thus gradually release them, providing a sustained immune response.
The researchers hypothesized that pexidartinab and PD-1 antibodies—delivered via the gel—could gradually deplete TAMs and strengthen T cells to better enable immune checkpoint inhibitor delivery drugs to prevent tumor regrowth.
Testing on colon, skin, and breast cancers
The researchers conducted experiments with the gel on mouse models of colon cancer, melanoma, and triple-negative breast cancer after surgically removing tumors.
After removing the tumors, they treated the mice with saline, a blank nanoparticle-loaded hydrogel (NP@Gel), PLX, PLX-nanoparticles (NP), or hydrogels containing PLX and NP (PLX-NP@Gel).
Overall, they found that mice treated with PLX-NP@Gel had up to 73.7% lower levels of TAMs and they also had 1.5-2.8 times more T cells than mice treated in other ways.
In models of melanoma, the researchers also found that mice treated with PLX-NP@Gel had 2.3 and 1.8 times less TAMs than mice treated with PLX alone of PLX-NP. The researchers say that delivering these drugs via hydrogel increases their efficiency due to gradual delivery.
PLX-NP@Gel also increased survival rates of mice with cancer. Whereas control animals survived for up to 36 days, the group of mice treated with the gel survived for 50–70 days.
‘Breakthrough’ potential
When asked whether the PLX-NP@Gel could be a breakthrough drug for cancer recurrence, Chao Wang, professor at the Institute of Functional Nano & Soft materials at Soochow University, China, who was not involved in the study, told MNT:
“It could be considered a potential ‘breakthrough’ for cancer treatment. But this ‘breakthrough’ potential still needs to be demonstrated in patients rather than in animal studies.”
Dr. Thompson agreed and added:
“[While these] results document the desired effects on the cellular makeup of the tumor microenvironment, […] Phase 1 clinical trials in cancer patients will be needed to identify side-effects, tolerability, and immunological effects of the hydrogel-delivered immunotherapy, and to begin to learn about anticancer effects in patients.”
The researchers concluded that aPD-1 antibody treatment could be strengthened by depletion of TAMS through a hydrogel.
When asked to comment on any limitations to the findings, Dr. Wang said:
“The limitations to the study may include a relatively complex system for further clinical translation and the clinical study of this approach in cancer patients.”
He added, however, that given high rates of recurrence in colon cancer, melanoma, and triple-negative breast cancer, these findings were “meaningful developments” towards preventing tumors from recurring.
“This approach may [also] inspire new ways for effective combination immunotherapy for these cancers,” he concluded.
Challenges lie ahead
Dr. Ashley Holder, assistant professor of surgical oncology at The University of Alabama at Birmingham, who was not involved in the study, told MNT that the gel’s utility might be limited:
”Hydrogel may provide a local recurrence risk benefit and help prime for response to immunotherapy but would have to be placed at the tumor site/resection bed which is typically completely removed during surgery for all these cancers, most of which is relatively unlikely to recur locally after surgery.”
However, she acknowledged that it may be useful in patients who are not well enough to tolerate surgery.
She further elaborated on some caveats:
“It may be difficult in colon cancer and melanoma to apply the gel to the tumor site/resection bed since it is completely resected. The hydrogel could be placed into the resection cavity of breast cancer if breast conservation is the approach selected. And if applied prior to resection, the efficacy of the gel in colon cancer would be limited by the flow of digested food through the GI tract and for melanoma, by covering it with a dressing to prevent the gel from being wiped away.”
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