- 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.
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
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.
The researchers conducted experiments with the gel on mouse models of colon cancer, melanoma, and triple-negative breast cancer after surgically removing tumors.
“It has been demonstrated that surgery could enhance the proliferation of tumor cells locally and in distant metastases, which is correlated with increased macrophage density in tumor tissues after surgery,” Dr. Quanyin Hu, assistant professor at the School of Pharmacy at the University of Wisconsin, one of the study’s authors, told MNT.
Dr. Hu said they chose colon cancer to represent the easy-to-treat hot tumors, melanoma to represent the hard-to-treat hot tumors, and triple-negative breast cancer to represent the hard-to-treat cold tumors. He said this multi-pronged approach helped show that the hydrogel treatment was a universal strategy.
After removing the tumors, the researchers 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.
When asked whether the PLX-NP@Gel could be a breakthrough drug for cancer recurrence, Dr. Chao Wang, professor at the Institute of Functional Nano & Soft materials at Soochow University, China, who was not involved in the study, spoke with MNT about the gel’s potential.
“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. Chao Wang
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” toward preventing tumors from recurring.
“This approach may [also] inspire new ways for effective combination immunotherapy for these cancers,” he concluded.
Dr. Hu said the gel could be adapted for other therapies as well.
“This gel could be adapted to other cell-based immunotherapy, such as adoptive T cell therapy and dendritic cell-based vaccination, making it of utmost interest to a broad scientific community,” he said.
“For example, given the current dilemma of CAR-T cell therapy against solid tumors in the clinic that is also hindered by [a] tumor-suppressive microenvironment, it can be easily envisioned that the developed local TAMs depletion strategy could be integrated to augment CAR-T cell therapy,” he explained.
Dr. Hu noted that a limitation of the hydrogel is that it does not have strong adhesive abilities, and hence, is “more suitable for implantation after resection of tumor lesions, such as muscle tissue or subcutaneous tissue.”
He said the gel was “not suitable for in situ tumor resection of some abdominal organs.”
Speaking to MNT, Dr. Ashley Holder, assistant professor of surgical oncology at The University of Alabama at Birmingham, who was not involved in the study, went into more detail about how 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.”