# Leveraging MR-Guided Focused Ultrasound  to Potentiate Immunotherapy  for GBM

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2020 · $208,881

## Abstract

Immunotherapy via checkpoint blockade could be an attractive option for Glioblastoma (GBM), a
disease with limited treatment options. A clinical response to checkpoint immunotherapy in other cancer
settings is often dependent upon a pre-existing immune infiltrate. However, glioblastoma is commonly poorly
infiltrated by effector immune cells. Thus, the translation of adjunct approaches that enhance T-cell infiltration
and/or lift the immunosuppressive tumor microenvironment could vastly expand the population of GBM patients
exhibiting durable responses to immunotherapy. Toward this goal, we hypothesize that perturbation of the
GBM microenvironment with focused ultrasound (FUS), applied in energy regimes designed to elicit partial
thermal ablation or microbubble cavitation, can stimulate immunologic responses that are both intrinsically
therapeutic and synergistic with translatable immunotherapies. Indeed, our pilot studies in melanoma indicate
FUS application can elicit tumor growth control and improved survival via trafficking of activated lymphocytes
from lymph nodes to the tumor.
 This proposal is comprised of 2 specific aims that will serve to define differences in the innate and
adaptive immune responses that are elicited by applying different FUS energy regimes to tumors, identify
barriers to tumor immunity, and ascertain treatment protocols that more effectively combine FUS energy
regimes with adjunct immunotherapies for treating GBM. Specific Aim 1 will be to determine the impact of the
selected FUS energy regimes on discrete factors that influence the sequential steps involved in the activation,
expansion, and recruitment of dendritic cells (DC) to the tumor microenvironment. Specific Aim 2 will be to
assess the ability of selected FUS regimens to promote the trafficking and extravasation of T cells into the
GBM tumor microenvironment, and ask whether hypothesis-driven selection of agents that promote trafficking
can augment T cell presence and persistence within tumors. This will allow us to understand barriers to
access for T cells expanded by vaccination or after adoptive transfer. Going forward, this will be a critical
aspect in optimizing the combination of FUS with anti-tumor immunotherapy. We believe the systematic and
directed approach proposed here is more likely to lead to successful clinical therapies for GBM patients with
limited T cell infiltration.

## Key facts

- **NIH application ID:** 10020956
- **Project number:** 5R21CA226607-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** TIMOTHY N BULLOCK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $208,881
- **Award type:** 5
- **Project period:** 2019-09-19 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020956

## Citation

> US National Institutes of Health, RePORTER application 10020956, Leveraging MR-Guided Focused Ultrasound  to Potentiate Immunotherapy  for GBM (5R21CA226607-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020956. Licensed CC0.

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