Nanoparticles at Specific Temperature Stimulate Antitumor Response
April 13, 2015
Dartmouth researchers identify precise heat to boost immune system against cancer tumors
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.
Fiering is Professor of Microbiology & Immunology, and of Genetics, at Dartmouth's Geisel School of Medicine. His work in cancer is facilitated by Dartmouth's Norris Cotton Cancer Center where he is a member of the Molecular Therapeutic Research Program.
Support for "Local Hyperthermia Treatment of Tumors Induces CD8+ T Cell-Mediated Resistance Against Distal and Secondary Tumors" was provided by the Dartmouth Center for Nanotechnology Excellence, National Institutes of Health grant 1 U54 CA151662, Center for Molecular, Cellular, and Translational Immunological Research grant NIGMS P20 RR15639, Norris Cotton Cancer Center Support Grant P30 CA023108 and Dartmouth Immunobiology of Myeloid and Lymphoid Cells grant 5T32A1007363-22.
About Dartmouth-Hitchcock Norris Cotton Cancer Center
Norris Cotton Cancer Center combines advanced cancer research at Dartmouth and the Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center in Lebanon, NH, at Dartmouth-Hitchcock regional locations in Manchester, Nashua, and Keene, NH, and St. Johnsbury, VT, and at 12 partner hospitals throughout New Hampshire and Vermont. It is one of 41 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.
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