Key Points
- Five preclinical projects have been initiated since April this year.
- Researchers are investigating focused ultrasound to change the microenvironment of various tumors, including glioblastoma, hepatocellular carcinoma, and breast cancer.
Five new Foundation-funded preclinical projects were launched in the second quarter of 2026. Projects in the Gene Therapy Program, the Brain Tumors Program, and the Immunotherapy Program are advancing research that uses focused ultrasound to improve therapeutic delivery to the brain, strengthen immune responses against cancer, and enhance the effectiveness of therapies for difficult-to-treat tumors.
“Each of these projects is designed to answer a key translational question, helping move focused ultrasound closer to combination therapies and delivery strategies that can expand treatment options for patients,” said Emily Whipple, PhD, the Foundation’s Strategic Initiatives Director. “By generating both mechanistic insight and translational evidence, these studies are helping build the scientific foundation needed for future clinical development.”
The guidelines for submitting a funding application to the Foundation are described below.
Gene Therapy Program (1)
Optimization of Focused Ultrasound Gene Delivery to the Brain for Clinical Translation: One-Time Administration Limitations led by Rikke Kofoed, PhD, at Aarhus University Hospital
Gene therapies may provide long-lasting benefits after a single treatment, but delivering these therapies to the brain is a challenge. The blood-brain barrier (BBB) protects the brain from harmful substances, but it also prevents many potentially beneficial treatments from reaching their target. Previous studies in mice and large animals have shown that focused ultrasound–mediated BBB opening (FUS BBBo) can significantly improve brain delivery of viral gene therapy delivery after systemic administration.
For this project, researchers will study whether the timing of adeno-associated virus administration relative to FUS BBBo affects gene delivery in the mouse brain. The team will assess how timing influences delivery efficiency, which cell types are transduced, and how far the therapy spreads from the site of entry. The findings will help optimize focused ultrasound–mediated gene delivery protocols for future clinical translation.
Brain Tumors Program (2)
Targeted Immunotherapy for Glioblastoma: Transcranial Focused Ultrasound–Mediated Delivery of STING Agonists via Nanocarriers led by Kristin Huntoon, DO, PhD, at the University of Arizona
Glioblastoma is an aggressive brain cancer with limited treatment options, in part because many drugs cannot efficiently cross the BBB. For this project, researchers will deliver an immune system-stimulating therapy called a STING agonist to glioblastoma tumors in mice using STING-laden Acousto-NanoDroplets (STANDs).
When activated by focused ultrasound, the STANDs are designed to simultaneously open the BBB and release a compound at the tumor site that activates a natural immune alarm pathway. The team will study whether this approach can help immune cells recognize and attack the tumor while limiting adverse effects.
Leveraging Focused Ultrasound and Focused Ultrasound–Mediated Transport to Enhance CAR T-Cell Therapy in Glioblastoma led by Jenny Munson, PhD, at Virginia Tech*
CAR T-cell therapy has been very successful in treating some cancers, but its use in brain tumors remains a challenge. One major obstacle is the BBB, which can limit the efficiency of CAR T cell delivery to the tumor.
In this project, researchers will test whether focused ultrasound can improve CAR T-cell delivery to glioblastoma in two ways: by improve the distribution of locally delivered CAR T-cells in the tumor tissue, and by opening the BBB to help intravenously infused CAR T cells enter the brain. If successful, this work could support focused ultrasound as a tool for improving cell therapy approaches for glioblastoma.
Immunotherapy Program (2)
Histotripsy-Induced Local and Abscopal Responses in Hepatocellular Carcinoma: Molecular Mechanisms and Synergistic Potential with Immunotherapy led by Tejaswi Worlikar, PhD, at the University of Michigan
Nearly two-thirds of patients with liver cancer have more than one tumor, and it is often not possible to directly treat every tumor. In this project, researchers will study whether combining histotripsy with immunotherapy can help treat both the tumor targeted by focused ultrasound and other liver tumors that are not treated directly. Histotripsy breaks apart tumor tissue without heat, which may release signals that help “wake up” the immune system. The team will test whether this effect can be strengthened with drugs that help immune cells attack cancer or improve the tumor environment. The findings may help show how focused ultrasound could do more than destroy individual tumors: It may also help the body recognize and fight liver cancer more broadly.
Expanding and Understanding the Efficacy of Combinatorial Thermally Ablative Focused Ultrasound, Vascular Normalization, and Immunotherapy led by Timothy Bullock, PhD, at the University of Virginia*
Immunotherapies that help the immune system attack cancer have produced meaningful results for many patients, but they do not work for everyone, including many patients with breast cancer. One reason for this may be that abnormal tumor blood vessels can limit immune cell access to tumors and reduce treatment effectiveness.
In this project, researchers will use mouse models of breast cancer to study whether drugs that improve tumor blood flow can help the immune system respond more effectively after focused ultrasound treatment. The team will test whether combining focused ultrasound thermal ablation with blood vessel–normalizing drugs and immunotherapy can improve treatment responses in difficult-to-treat tumors.
*This project was funded by the Commonwealth of Virginia as a result of the Foundation’s advocacy efforts.
Applicant Guide
The Foundation’s Research Funding Applicant Guide describes its research priorities, two-part application process, what happens after a funding decision is made, and a Q&A on how to write a Letter of Intent, or LOI.