Immunotherapy is hailed as the defining cancer treatment breakthrough of the 21st century. But its impact has been limited, especially for patients with breast cancer. Researchers at UVA Health are working to tackle these limitations by combining immunotherapy with focused ultrasound (FUS) tumor ablation.
UVA Health has been a pioneer in advancing clinical applications for FUS, a non-invasive technology that delivers non-ionizing soundwaves. And now UVA Health is extending its use further by establishing the world’s first Focused Ultrasound Cancer Immunotherapy Center.
Advancing breast cancer treatment is a key part of the new center’s focus.
“With this combination, we’re actually intentionally not destroying the whole tumor. Instead, we’re trying to use the heat radiation from the tissue that’s been ablated by FUS to essentially change the microenvironment of the tumor, and make it more likely to be receptive to an immunotherapy drug that’s being delivered,” explains Richard J. Price, PhD, co-director of the new center and the Nancy and Neal Wade Professor of Biomedical Engineering.
Helping More Patients Respond to Checkpoint Inhibitors
Patients who have immunologically “hot” tumors — like lung cancers, melanomas, and renal cell cancers — have immune systems primed to attack the cancer. But most breast cancers are immunologically “cold.” Less than 20% of breast cancers, in fact, respond to immune checkpoint inhibitors, and these are mostly triple-negative breast cancers, says David Brenin, MD, who also codirects the Focused Ultrasound Cancer Immunotherapy Center.
He’s collaborating on 2 UVA Health-developed clinical trials investigating FUS tumor ablation for the treatment of breast cancer.
Patrick Dillon, MD, in the UVA Health division of hematology/oncology, is the principal investigator for both trials.
Trial: FUS & Pembrolizumab in Metastatic Breast Cancer
The researchers set out to determine if they could change the tumor microenvironment to “hot” in other types of breast cancer if they combined focused ultrasound with the checkpoint inhibitor pembrolizumab.
“We know that pembrolizumab is able to induce an immune response to some breast cancers, and that focused ultrasound ablation is able to induce an immune response in most tumors but not enough to be curative,” Brenin says. “So we’re hoping to answer, 'Might the combination be effective?’”
The clinical trial is now closed.
Trial: FUS & Gemcitabine in Breast Cancer
Currently recruiting patients, a second clinical trial is evaluating the combination of focused ultrasound ablation with low-dose gemcitabine in patients with early-stage breast cancers.
The goal is to decrease myeloid-derived suppressor cells, which subdue the immune response in tumors, and increase T-cell activity.
In the randomized trial:
- A third of patients receive gemcitabine followed by surgery
- A third of patients receive focused ultrasound ablation followed by surgery
- A third of patients receive gemcitabine followed by focused ultrasound ablation followed by surgery
“The aim is to induce a measurable systemic immune response that, hopefully, improves survival by recruiting the patient’s immune system to fight any cancer cells that have escaped from the tumor and spread,” Brenin says.
This abscopal effect occurs when a localized therapy – in this case, focused ultrasound ablation — not only shrinks the targeted tumor but also causes tumors elsewhere in the body to shrink.
“It is our hope that focused ultrasound ablation has the potential to be both a local and a systemic therapy,” Brenin says.