Researchers test noninvasive cancer treatment to trigger body's immune defenses
Histotripsy not only works against targeted tumors, but may also trigger an immune response against tumors elsewhere in the body.
That was a finding in the 2018 Theresa Study, the first-ever trial of histotripsy — a noninvasive tumor-destruction technique using focused ultrasound waves — in human patients.
Now, new research led by Virginia Tech seeks to take that discovery a step further.
This research, funded by a $419,080 grant from the National Cancer Institute, combines histotripsy with an immune-stimulating compound to treat osteosarcoma, an aggressive bone cancer that carries a grim prognosis for people and dogs.
"I had never even hypothesized that tumors we didn't treat might potentially shrink in size because of this immune response," said Eli Vlaisavljevich, the Kendall and Laura Hendrick Junior Faculty Fellow in the College of Engineering and associate professor of biomedical engineering. "It was shocking to be in that trial and actually see what we refer to as abscopal effects."
The 2018 study focused on liver cancer, which claimed the life of Vlaisavljevich’s mother Theresa, the namesake of the study. The new research focuses on a different but also deadly cancer.
"The survival outlook for osteosarcoma has not improved in decades, whether it's for people or dogs, and so it would be really motivating to be able to have a chance to change that," said Joanne Tuohy, associate professor of surgical oncology with the Virginia-Maryland College of Veterinary Medicine at Virginia Tech, who is the principal investigator for the grant and leads clinical trials for dogs with osteosarcoma.
The newly funded study will combine histotripsy with IP-001, a polymer developed by Immunophotonics that can be injected to help the body's immune system recognize and attack cancer cells throughout the body.
Histotripsy uses precisely focused ultrasound waves to mechanically disintegrate tumor cells without incisions, radiation or heat, making it the first completely noninvasive, non-thermal tumor ablation method.
But the therapy appears to do more than simply destroy the tumor it targets.
Researchers have observed what is known as an abscopal effect — a phenomenon in which untreated tumors elsewhere in the body shrink following histotripsy treatment of the primary tumor. The leading explanation is that debris left behind after histotripsy acts as a kind of alarm signal, prompting the immune system to recognize and attack surviving cancer cells throughout the body.
"The effects of histotripsy are broader than what was initially anticipated," Tuohy said.
For dogs with osteosarcoma, the current standard of care is amputation of the affected limb followed by systemic therapy.
Researchers hope histotripsy can become an alternative for dogs, then ultimately translate into an effective treatment of human osteosarcoma.
The possibility emerged during the Theresa Study. In several late-stage patients, tumors that were never directly treated shrank in size following the procedure.
That discovery shaped the current research, which pairs histotripsy with immunotherapy on the theory that the two treatments can amplify each other. Osteosarcoma has historically resisted immunotherapy when used alone, but researchers believe histotripsy may give those drugs the foothold they need.
"We can use the histotripsy to stimulate that immune response first, and then when we add an immunotherapy to it, we give the immunotherapy that initial boost, so that immunotherapy can, we hope, now be effective," Tuohy said.
Canine osteosarcoma is biologically nearly identical to the human version, and pet dogs are large enough that the treatment devices scale directly to human applications. They also occupy the same environments as their owners.
"Our pet dogs — they live with us,” Tuohy said. “They have very similar immune systems."
Virginia Tech has been running canine clinical trials for histotripsy since 2020, funded by the National Institutes of Health, the Focused Ultrasound Foundation and the Veterinary Memorial Fund, in addition to the new grant. Parallel mouse studies examine the biological mechanisms driving the immune response.
Much of the day-to-day work is being driven by graduate students and postdoctoral research scientists in the Therapeutic Ultrasound and Non-Invasive Therapies Laboratory guided by Vlaisavljevich and the Comparative Oncology Research Laboratory led by Tuohy at the Animal Cancer Care and Research Center in Roanoke.
Vlaisavljevich said the goal is to accumulate enough data to support a larger, controlled trial comparing histotripsy alone, immunotherapy alone, and the combination.
