Cancer: How a novel gel could halt its return

Groundbreaking research has revealed a promising strategy to stop the recurrence of cancer, and it comes in the form of a biodegradable gel.

Created by scientists at the Dana-Farber Cancer Institute in Boston, MA, the gel was designed to deliver immunotherapy directly to the area from which a cancerous tumor has been surgically removed.

Upon testing the gel on mice during the surgical removal of breast cancer tumors, the scientists found that it not only helped to prevent tumor recurrence at the primary site, but that it also eliminated secondary tumors in the lungs.

Senior study author Michael Goldberg, Ph.D. — of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute — and colleagues recently reported their results in the journal Science Translational Medicine.

According to the American Cancer Society (ACS), more than 1.7 million new cancer cases will be diagnosed in the United States in 2018, and over 600,000 people will die from the disease.

For cancer that forms as solid tumors — such as breast cancer and lung cancersurgical removal of the tumor is often the primary treatment option.

The problems with immunotherapy

However, as Goldberg explains, even when the tumor is removed, some cancer cells may remain at the site. These can form new tumors, or even spread to other areas of the body. This is a process known as metastasis.

"Indeed, while half of all cancer patients undergo surgery aiming to cure the disease, 40 percent of such patients experience a recurrence of the disease within 5 years," Goldberg notes.

"Furthermore," he adds, "it has been shown that the body's natural process of healing the wound created by surgery can actually spur these residual cancer cells to metastasize to distant parts of the body and form new growths."

Immunotherapy — which involves using drugs to stimulate the immune system and attack cancer cells — can help to prevent cancer recurrence and metastasis. However, the treatment has some serious pitfalls.

A major problem with immunotherapy is that it can attack healthy cells as well as cancerous ones, which can increase a patient's susceptibility to other illnesses.

"In this study," notes Goldberg, "we sought to determine whether administering immune-stimulating drugs at the [right] place and the right time — at the site of tumor removal, before the surgical wound has been closed — could enhance the results of cancer immunotherapy."

The path to 'immunostimulation'

The researchers explain that when a cancerous tumor is removed, the immune system uses most of its resources to help heal the wound, rather than fighting any cancer cells that may have been left behind.

This can create what the team calls an "immunosuppressive" microenvironment, in which cancer cells can thrive and spread.

As Goldberg explains, the scientists set out to transform this immunosuppressive microenvironment into one that is "immunostimulatory" — that is, one that can attack and destroy residual cancer cells after surgery.

To achieve this feat, the researchers created a hydrogel loaded with drugs that stimulate dendritic cells, which are immune cells that are involved in the initial immune response. They "present" any foreign invaders or diseased cells — such as cancer cells — to T cells, which launch an attack.

The gel — which comprises a sugar naturally present in the human body, making it biodegradable — is placed at the site from which a tumor has been surgically removed. The gel then gradually releases the drugs over a prolonged period, which the team says increases its efficacy.

'Encouraging' results

For their study, Goldberg and team tested the gel in mice that underwent the surgical removal of breast cancer tumors. The team made the decision to use the gel directly after tumor removal, rather than before.

"We reasoned," Goldberg explains, "that it would be easier to eliminate a small number of residual cancer cells by creating an immunostimulatory environment than it would be to treat an intact primary tumor, which has many means of evading an immune system attack."

Several months after surgery, the mice treated with the gel were much less likely to experience tumor regrowth, compared with rodents that received conventional immunotherapy delivery.

When the researchers injected breast cancer cells into the side opposite to where the original tumor was removed, the gel-treated rodents showed no signs of tumor formation.

Also, the study found that the gel eradicated secondary tumors in the lungs of the mice — that is, it eliminated lung tumors formed from breast cancer cells that had spread from the primary site.

The researchers also replicated their findings in mice with primary lung cancer and melanoma, which is a deadly form of skin cancer.

Based on their results, Goldberg and colleagues believe that their gel-based immunotherapy could be an effective treatment strategy against a number of different cancers.

"This approach has the potential to deliver immunotherapy in a manner that focuses the therapy at the site of interest during a critical time window," he says.

"We are extremely encouraged by the results of this study and hope that this technology will be adapted for patients for testing in clinical trials in the not-too-distant future."

Michael Goldberg, Ph.D.