Researchers develop cancer therapy

by Emily Goodell | 7/23/09 10:00pm

Two Dartmouth Medical School immunologists have designed a new method of treating ovarian cancer through the injection of nanoparticles. The research, done by Jose Conejo-Garcia, a professor of microbiology and immunology at Dartmouth Medical School, and microbiology and immunology graduate student Juan Cubillos-Ruiz DMS '10, was published in the online Journal of Clinical Investigation July 13.

Cubillos-Ruiz and Conejo-Garcia found that by injecting tiny nanoparticles into the abdomens of mice that had confirmed cases of ovarian cancer, they could cause certain cells to attack and kill tumor cells, increasing the life expectancy of the mice, Cubillos-Ruiz said in an interview with The Dartmouth.

Nanoparticles are defined as any piece of matter that is less than 100 nanometers in size, Cubillos-Ruiz said. Cubillos-Ruiz and Conejo-Garcia created nanoparticles about 15 nanometers in size that consisted of small pieces of RNA surrounded by a polymer, Cubillos-Ruiz said.

When ovarian cancer infects the body, it takes over dendritic cells and represses their natural activity. Normally, dendritic cells are "soldiers of the immune system," Cubillos-Ruiz said, but when they come into contact with tumor cells, they become destructive.

"The ovarian cancer actually recruits the dendritic cells from your body into the peritoneal cavity where the tumors are, and what happens is that these dendritic cells become very bad cells," he said. "Instead of being cells that help the immune system, they end up being cells that contribute to the growth of the tumors."

That is where nanoparticles are used, Cubillos-Ruiz said. Dendritic cells are phagocytes, which means they have the ability to absorb other cells and bacteria. Thus, when the dendritic cells come into contact with nanoparticles, they absorb them.

Each nanoparticle contains "small interfering" bits of RNA, known as siRNA, which affect the cell's behavior after they are absorbed, Cubillos-Ruiz said. With siRNA, researchers can "reprogram" dendritic cells to make them helpful instead of destructive, causing them to attack tumor cells.

Furthermore, when the immune system's T-cells come into contact with the dendritic cells affected by the nanoparticles, they are activated, further strengthening the body's immune response, Cubillos-Ruiz said.

Nanoparticles have been used before in cancer treatments, Cubillos-Ruiz said, but in the past the focus has always been on using them to affect the tumor cells themselves. This study is the first study in which the nanoparticles were used on dendritic cells, which was much more effective because dendritic cells tend to absorb large numbers of nanoparticles, while tumor cells do not, Cubillos-Ruiz said.

Nanoparticles are especially effective as a means of fighting ovarian cancer because it is possible to inject them directly into the peritoneal cavity, located in the abdomen.

"For other types of cancer, you have to inject them through your veins, and the problem is that when you do that, all the nanoparticles will go to the lungs, the kidneys, the liver, which can be harmful," Cubillos-Ruiz said.

In addition to testing the nanoparticle treatment on mice, the researchers tested it on human tumor tissue, Cubillos-Ruiz said, and found it to be effective. Since the publication of the article, many people suffering from ovarian cancer have called asking about clinical trials for the treatment, he said.

"These people are very desperate to get a new treatment because they have the ovarian cancer that is recurrent and also that is resistant to chemotherapy, so they're very interested in these new strategies and new approaches," Cubillos-Ruiz said.

Nanoparticle treatment is a good compliment to current treatments for ovarian cancer, which include surgery and chemotherapy, Cubillos-Ruiz said, because it targets cells surrounding the cancer cells, not just the tumor cells themselves.

"It is a new way of treating the cancer without actually touching the tumor cells," he said. "This opens up the door for researchers who want to treat ovarian cancer using the immune system."

Ovarian cancer kills an estimated 15,000 Americans each year, according to the press release.

The article in the Journal of Clinical Investigation was co-authored by Cubillos-Ruiz and Conejo-Garcia, as well as several other researchers from the University of New Hampshire, Emory University and the University of Colorado. Cubillos-Ruiz is the article's first author. Conejo-Garcia could not be reached for comment by press time.