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Published on: March 18, 2014
Immunological and Clinical Outcomes Associated with Histotripsy Ablation in Spontaneously Occurring Canine
Alayna N Hay1,2, Lauren Ruger3, Elliana R Vickers1,3,4
1Department of Small Animal Clinical Sciences, Virgina Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA.
Background:
Osteosarcoma (OS) is a devasting bone cancer that occurs primarily in pediatric patients, and pet dogs, and treatment options have not advanced in decades. There is a profound need for advancement of treatment options to improve patient prognosis given the grim 70% 5-year survival rate for human patients, and 10-12-month median survival for canine patients. A major hurdle in advancing treatment options is overcoming the immunosuppressive tumor microenvironment to mitigate metastatic disease progression-the leading cause of mortality in OS patients.
Methods:
We investigated the ability of a mechanical focused ultrasound ablation modality, histotripsy, to induce acute immunomodulation in canine patients with spontaneously occurring OS.
Results:
Immunomodulation was evident locally and systemically. Tumor gene signatures indicated upregulation of pro-inflammatory signaling pathways and T-cell receptor signaling, and B-cell activation, and systemically, increased monocyte activation was observed within 5 days post-histotripsy ablation. A subset of patients who received histotripsy prior to definitive standard-of-care exceeded the reported expected median survival time of 10-12 months for canine OS patients that received definitive standard-of-care only.
Conclusions:
Our results demonstrate the promising potential of histotripsy to overcome the immunosuppressive tumor microenvironment.
Insights
Histotripsy, a focused ultrasound technique, shows promise in treating osteosarcoma (OS) by modulating the tumor microenvironment. This approach may improve survival times for canine OS patients, offering new hope for this devastating bone cancer.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Osteosarcoma (OS) is a rare bone cancer affecting children and dogs with poor prognoses.
- Current OS treatments have stagnated, necessitating novel therapeutic strategies.
- The immunosuppressive tumor microenvironment hinders treatment efficacy and promotes metastasis in OS patients.
Purpose of the Study:
- To investigate histotripsy's potential to induce immunomodulation in canine OS.
- To assess the impact of histotripsy on the tumor microenvironment and systemic immunity.
Main Methods:
- Utilized histotripsy, a mechanical focused ultrasound ablation, in canine patients with naturally occurring OS.
- Analyzed tumor gene expression and systemic immune cell activation post-ablation.
Main Results:
- Histotripsy induced local and systemic immunomodulation, including pro-inflammatory signaling and immune cell activation.
- Observed increased T-cell and B-cell signaling, alongside enhanced monocyte activation within five days.
- Canine patients receiving histotripsy before standard care showed improved survival beyond the expected median.
Conclusions:
- Histotripsy demonstrates potential in overcoming the immunosuppressive tumor microenvironment in OS.
- This modality may offer a novel therapeutic approach to improve outcomes for OS patients.

