Investigation of the immunostimulatory response to mechanical high intensity focused ultrasound (histotripsy) in dogs with naturally-occurring soft tissue tumors

Project Name: Investigation of the immunostimulatory response to mechanical high intensity focused ultrasound (histotripsy) in dogs with naturally-occurring soft tissue tumors
Status: Active
Primary Site: Virginia-Maryland College of Veterinary Medicine
Sponsor Organization: Focused Ultrasound Foundation
Funded Date: Apr 07, 2020
Funding Period: Apr 07, 2020 - Apr 07, 2021
Funding Program: Veterinary
Category: Vet
Amount Awarded: $162,460.00

Abstract

Histotripsy is a precision, non-thermal high-intensity focused ultrasound (HIFU) ablative technique that results in mechanical disintegration of tissue, disruption of cell membranes, and release of intracellular contents. Histologically, there is a clear demarcation between treated tissue and non-treated tissue, without altering the state of large blood vessels. The cell debris of the histotripsy field contains non-denatured proteins, including potential cancer neoantigens. Rodent xenograft and in vitro studies have demonstrated that HIFU is immunogenic, and studies report a more robust immune response and decreased rate of metastasis following histotripsy compared to thermal HIFU. The mechanism of immune stimulation of thermal and mechanical HIFU has yet to be fully understood, and differences may be related to the type or level of danger signals released during treatment. Additionally, current studies have evaluated the impact of HIFU on immune stimulation, but there is little known regarding the release of or effect on inhibitory immune signaling. Solid tumors, including soft tissue sarcomas, are a common form of cancer in dogs. They are locally invasive into surrounding tissues and complete removal requires extensive surgical resection, which in many cases is impossible. Without complete removal, local recurrence is common. Soft tissue sarcomas are much less common in humans, but the biological behavior is similar in both species. There is significant need for alternative or adjuvant local therapies, and immunotherapy is an attractive option to address the microscopic disease. The naturally-occurring tumors in dogs present an opportunity for discovery and investigation of treatments with translational potential.

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