Nanoparticles at specific temperature stimulate antitumor response

Seeking a way to stimulate antitumor responses via the immune system, Steven Fiering, PhD, of Norris Cotton Cancer Center at Dartmouth, has identified the precise temperature that results in a distinct body-wide antitumor immune response that resists metastatic disease. Fiering's team published the research in the paper "Local Hyperthermia Treatment of Tumors Induces CD8+ T Cell-Mediated Resistance Against Distal and Secondary Tumors," which appeared in Nanomedicine: Nanotechnology, Biology and Medicine.

"Mild hyperthermia treatment of an identified tumor, prior to surgery to remove the tumor, shows excellent promise to strengthen the antitumor response and help stop metastatic disease," explained Fiering.

Among the many options for cancer treatment pursued by science, immunotherapy is a contemporary focus. The immune system recognizes and usually eliminates small tumors, but other tumors become clinical problems and are known to block the antitumor tendencies with a natural system for immunosuppression. Recently, scientists have worked to learn how to reverse this tumor-mediated immunosuppression. In addition, phagocytes (key actors in immunosuppression and immunostimulation and that quickly take up nanoparticles) have provided options for new strategies. Fierings's studies were done in mice with a melanoma tumor model, and began with inserting iron nanoparticles directly into the tumors while applying an alternating magnetic field to heat the nanoparticles evenly and at precise temperatures.

"While it's easy to apply enough heat to destroy the tumor, that sort of thermal ablation does not have the result we were looking for, which was to stimulate a systemic immune response to eliminate metastatic disease," said Fiering. "Looking at temperature variables, we learned that at precisely 43 degrees centigrade, the systemic immune response goes into action. Doing this safely is a potent treatment approach that can stimulate the immune system to fight untreated metastatic tumors."

Fiering utilized Dartmouth's Shared Resources including the Transgenic Mouse Resource to do mouse manipulations. Colleague P. Jack Hoopes of Dartmouth's Thayer School of Engineering provided the vitally important alternating magnetic field equipment. The Dartmouth Shared Resources are open to outside investigators by arrangement.

Using Norris Cotton Cancer Center's team science approach, Fiering and Hoopes look forward to joint studies testing the systemic immune response to nanoparticle treatment in dogs with melanoma. As in humans, melanoma is frequently metastatic and fatal for dogs. If the systemic immune response can be shown to prevent metastatic disease in dogs, it will be ready to develop for human clinical trials.