Therapeutic Nanoparticles Found To Induce an Effective Antitumor Immune Response at a Specific Temperature

Therapeutic Nanoparticles Found To Induce an Effective Antitumor Immune Response at a Specific Temperature

Researchers at the Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center and the Wistar Institute have discovered the exact temperature at which a cancer immunotherapy strategy based on nanoparticles induces an effective antitumor immune response. The study was published in the journal Nanomedicine: Nanotechnology, Biology and Medicine and is entitled “Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors.

The body’s immune system is able to recognize and destroy small tumors; however, some cancers can block the antitumor response by an immunosuppressive action. Researchers have focused on possible immunotherapeutic strategies to reverse this tumor-mediated immunosuppression.

Nanotechnology has allowed significant advances in the field of cancer detection and treatment. Iron oxide nanoparticles in particular were one of the first nanomaterials applied in the field of oncology. They have magnetic properties and when exposed to an alternating magnetic field, they spin, generating significant heat. If these nanoparticles are inside a tumor cell, they can actually destroy the malignant cells by heat therapy, also called cancer hyperthermia.

“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,” said the study’s senior author Dr. Steven Fiering in a news release.

The research team conducted studies in a rodent model of melanoma (the most dangerous form of skin cancer, often metastatic) using tumor-targeted iron nanoparticles and by applying an alternating magnetic field to heat the nanoparticles evenly at defined temperatures.

Researchers found that heating primary melanoma tumors treated with iron oxide nanoparticles for 30 minutes at 43 °C resulted in the activation of specific immune cells (namely dendritic cells and CD8+ T cells) and conferred resistance against tumor re-challenge (secondary tumors). Curiously, no resistance to re-challenge was observed when primary tumors were treated at 45 °C.

“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,” explained Dr. 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.”

The research team concluded that the combination of iron oxide nanoparticles and alternating magnetic fields can result in local hyperthermia in tumors in a controlled and uniform manner. The authors emphasize that a precise temperature of 43 °C allows a distinct body-wide antitumor immune response resistant to recurrence and metastatic disease.

The team’s next goal is to evaluate the systemic immune response to nanoparticle therapy in dogs with melanoma. In case the immune response triggered in dogs is shown to be capable of preventing metastatic disease, then the team can test this strategy in human clinical trials.