Research Awards Update: Five Preclinical Projects Initiated in the Third Quarter of 2023

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Key Points

  • The Foundation’s Research Awards Program initiated five preclinical studies since July. 
  • The funded projects are studying the use of focused ultrasound for brain tumors, cancer immunotherapy, osteosarcoma, and renal cell carcinoma. 

The Foundation’s Research Awards Program initiated five new preclinical studies in the third quarter of 2023. The funded projects are studying the use of focused ultrasound for brain tumors, cancer immunotherapy, osteosarcoma, and renal cell carcinoma. 

The newly initiated projects are listed below. 

Brain Technical 

Noninvasive Debulking of Brain Tumors led by Kevin Lee, PhD, a neuroscientist at the University of Virginia School of Medicine 
For this project, researchers will develop a novel, noninvasive strategy for debulking glioblastomas (GBMs) to reduce their size. The alternative approach will use low-intensity, magnetic resonance–guided focused ultrasound to enhance delivery of an intravenously-administered compound that is toxic to both glioblastoma stem cells and glioblastoma cells. The goal of the debulking is to prolong survival and limit side effects. 

Cancer Immunotherapy 

Focused Ultrasound–Mediated Delivery of DNMT1-Inhibiting Nucleic Acids to the Tumor Endothelium led by Katie Gorick, PhD, in the Price Laboratory at the University of Virginia 
Researchers are seeking to determine whether focused ultrasound–mediated transfection of the vascular endothelium can alter T cell trafficking. To test the hypothesis that the tumor endothelium is a rich target for immunotherapeutic modulation, the group will use focused ultrasound plus microbubbles to deliver nucleic acids that could reprogram the tumor endothelium. 

Augmenting Focused Ultrasound–Mediated Drug Delivery to Brain Tumors with Vascular Normalization led by Rich Price, PhD, at the University of Virginia 
Vascular normalization strategies create windows of time for optimal drug delivery. Depending on the approach, windows may open as soon as a few days after starting treatment, and closure time depends on many factors. To determine how vascular normalization approaches affect focused ultrasound–induced blood-brain barrier opening and blood-tumor barrier opening, researchers are investigating whether optimal vascular normalization windows for another method (enhanced permeability and retention–mediated delivery) coincide with the focused ultrasound plus microbubble–mediated delivery method. 

Veterinary Program 

Advancing Histotripsy Toward Clinical Translation for Focused Ultrasound Ablation of Osteosarcoma led by Joanne Tuohy, DVM, PhD, DACVS, at the Virginia-Maryland College of Veterinary Medicine 
To compare histotripsy and thermal ablation for treating osteosarcoma, researchers will measure the immunomodulatory effects between histotripsy and thermal high-intensity focused ultrasound ablation of osteosarcoma in a mouse model. They will then use a canine patient comparative oncology model to evaluate the effects of histotripsy ablation of osteosarcoma in that model. 

FUS Scholars Program 

Advancing Boiling Histotripsy Dose Proof of Concept in Ex Vivo and In Vivo Models Toward the Treatment of Renal Cell Carcinoma led by Ekaterina Ponomarchuk, MS, and supervised by Tatiana Khoklova, PhD, at the University of Washington and Moscow State University 
This project aimed to determine dosing for using boiling histotripsy for noninvasive mechanical ablation of renal cell carcinoma. In vivo and ex vivo porcine and canine models were used to measure tissue resistance to mechanical fractionation based on stiffness, tissue composition, structural arrangement, degree of perfusion, water content. 

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