Immunological and Clinical Outcomes Associated with Histotripsy Ablation in Spontaneously Occurring Canine Osteosarcoma; Veterinary Clinical Trial Results.
In a veterinary clinical trial of dogs with spontaneous osteosarcoma, histotripsy ablation was associated with local and systemic immune activation, while a subset treated before standard care survived beyond the reported historical median for canine disease.
Open original publication →What the AI sees
In a veterinary clinical trial of dogs with spontaneous osteosarcoma, histotripsy ablation was associated with local and systemic immune activation, while a subset treated before standard care survived beyond the reported historical median for canine disease.
Research significance
The record provides evidence that histotripsy is followed by pro-inflammatory and adaptive immune signaling in canine osteosarcoma; it supports, but does not establish, the hypothesis that histotripsy could remodel the immunosuppressive tumor microenvironment and improve systemic or survival outcomes when combined with standard therapy in canine or pediatric osteosarcoma.
Source abstract
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.