A team of scientists led by a researcher at Case Western Reserve University recently received a $3 million grant from the National Cancer Institute (NCI) to support their work combining nanotechnology with immunotherapy to fight deadly metastatic breast cancer.

The novel technique sends nanoparticles into the body to wake up "cold" tumors so they can be located and then neutralized by immune cells, according to a news release.

Immunotherapy uses drugs to help the immune system fight cancer, rather than chemotherapy, which uses drugs to kill cancer cells. Nanotechnology manipulates matter at the nanoscale (dimensions measured by nanometers or one-billionth of a meter) to create structures, devices and systems for medical uses and beyond, according to the release.

Efstathios "Stathis" Karathanasis, an associate professor of biomedical engineering at CWRU, is leading the team, which includes researchers from Cleveland Clinic and Duke University.

The five-year grant supports the team as it continues its research, initially on animal models with an eye toward human trials. Much of the groundwork behind the project has been published in a paper in Cancer Research, the official journal of the American Association for Cancer Research.

"We believe our work shows that this combination of nanotechnology with cancer immunotherapy encompasses an inherent promise to treat the most hard-treat metastatic cancers," Karathanasis said in a provided statement. "Our work has been to design a nanoparticle that triggers an activation of antigen-presenting cells in the tumor. Within a few weeks, the patient can have adapted T cells that recognize and fight the cancer."

Breast cancer, which causes more than 42,000 deaths a year, is the second-leading cause of death from cancer in women in the United States; skin cancer is the first. Also called stage IV cancer, metastatic breast cancer causes the vast majority of those deaths. It is breast cancer that has spread to another part of the body most commonly, the liver, brain, bones or lungs, according to the release.

Metastatic cancer cells are often considered stealth killers, "ticking time bombs that remain dormant until they emerge as incurable tumors," said Karathanasis, an engineer by training who began work on nanotechnology solutions to medical problems about two decades ago.

One of the most difficult aspects of diagnosing and treating metastatic breast cancer is that cells often cannot be found until it's too late for successful treatment, according to the release. Though the science continues to develop and offer hope for cancer patients, immunotherapy is only successful about 20% of the time. When it works, it's "highly effective," Karathanasis said in the release.

"But cancer cells hijack and recruit the local immune cells in tumors making them dysfunctional, unfortunately," Karathanasis said. "If there are no danger signals from the body, the immune system doesn't know there is an enemy."

When a tumor appears in the body, immune cells should recognize it and send out cells to try to kill it, as well as "memorize" it, so they can come back and kill it again in recurrences, Karathanasis said in the release. But tumors adapt and repress immune cells so the immune system can't find it.

Karathanasis has developed a way to get the tumor to notify the body's immune system of its presence, according to the release. The team have engineered a nanoparticle to "trigger the antigen-presenting cells in the tumor to start generating fresh signals," he said.

"We are unlocking the immune system, which has been repressed by the tumor," Karathanasis said. "We regenerate the cycle of immunity."

The research team also includes, according to the release: William Schieman, the Goodman-Blum Professor in Cancer Research at Case Western Reserve School of Medicine; Li Lily Wang, associate staff at Cleveland Clinic Lerner Research Institute; and Christopher Hoimes, of Duke University School of Medicine.

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CWRU-led research team receives $3 million grant to fight breast cancer with nanotech, immunotherapy - Crain's Cleveland Business