Two of the biggest obstacles to surviving cancer after surgery to remove the primary tumor are that the tumors tend to come back, and worse, they spawn distant metastases that are difficult to treat. Scientists at Dana-Farber Cancer Institute and Harvard have invented an immunotherapy “gel” that can be placed at the tumor site during surgery that’s designed to combat both problems.
The gel, made of biodegradable sugar, contains drugs that activate cells in the immune system called dendritic cells. These cells are important because they train T cells to attack cancer cells—even those far beyond the site of the original tumor. The gel releases the drug over a long period of time, according to a press release from Dana-Farber.
Early studies in animals look promising. In a study in mouse models of breast cancer, the team removed tumors and placed the gel at the surgery site. Over the next three months, more of the mice were cured with this technique than with standard treatments, they reported in the journal Science Translational Medicine. The breast tumors did not recur, and the treatment eliminated metastases in the lungs. Even when they implanted new breast cancer cells into the mice, the disease didn’t recur—a sign that the immune system was still actively combating the cancer. The findings were repeated in mice with melanoma and lung tumors, the Dana-Farber researchers said.
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If the gel works in people, it could be significant, because 40% of cancer patients who undergo surgery relapse within five years, noted senior author Michael Goldberg, Ph.D., assistant professor at Dana-Farber and Harvard Medical School, in the release. "Even when an entire tumor has been removed, it is common for a small number of tumor cells to remain behind,” he said. In fact, the surgery itself can create problems, by prompting those residual cancer cells to travel to other sites in the body.
And immuno-oncology drugs like checkpoint inhibitors, which allow the immune system to recognize and attack cancer, aren’t effective in all patients. An implantable gel could bring the treatment mode to a wider patient base, Goldberg believes. “The ability to address any solid tumors that can be surgically removed greatly increases the number of patients who might benefit from such potent immune-stimulating agents,” he said.
The news comes on the heels of an announcement from Novartis that it is teaming up with Harvard to explore ways to use biomaterials developed by scientists at the university to develop new cancer vaccines.
Stanford is also working on technologies aimed at stimulating immune cells at the tumor site. In February, Stanford scientists published research on their approach, which involves injecting an antibody and a short segment of DNA directly into tumors. It’s showing early promise in animal models of lymphoma, breast cancer, colon cancer and melanoma.
The Dana-Farber scientists believe their gel is well-suited to patients who have undergone surgery to remove tumors, because surgical wounds are naturally “immunosuppressive”—meaning the body is so focused on healing the wound that the immune system isn’t as effective at guarding against cancer. The gel, they say, transforms the surgical site into an “immunostimulatory environment.” They are now working on adapting the technology for testing in people.