# High-frequency Irreversible Electroporation (H-FIRE) combinatorial GBM treatment

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $353,192

## Abstract

Project Summary
This project will culminate in the development of a combinatorial therapy that enhances high-frequency
irreversible electroporation (H-FIRE) focal ablation, surpassing traditional therapies in terms of ability to
selectively target infiltrative cells beyond the tumor margin of glioblastoma (GBM). H-FIRE is a new,
minimally invasive ablation technique that involves delivering a series of electric pulses that are low in
energy, but intense (~1000 V) and short (~1 us) to targeted tissue for approximately 5 minutes. These
pulses destabilize the cell membranes of the targeted tissue, inducing cell death without causing thermal
damage. H-FIRE creates complete and predictable cell ablation with a sharp transition between normal
and necrotic tissue. Furthermore, H-FIRE preserves important tissue components such as extracellular
matrix, myelin sheaths, blood vessels, connective tissue, and nerves. We hypothesize that infiltrative cells
(beyond the H-FIRE treated zone) can be selectively killed using a low dose of an anti-GBM drug in
combination with H-FIRE, resulting in complete regression of tumors while preventing infiltration beyond
the tumor margins. For tumor cells outside the zone of tissue ablation, there is a non-destructive increase
in blood-brain barrier permeability, thus, making them more susceptible to the administered agents and
thus making the combination of IRE and adjuvant agents synergistic. By focusing on brain cancer, we will
be directly addressing the need to develop alternative approaches to radiation and chemotherapy, both of
which have adverse side effects and limited efficacy. The project has three Specific Aims. In Aim 1, we will
develop optimized treatment parameters for H-FIRE targeting penetration into the infiltrative niche of GBM,
with a combination of H-FIRE and delivery of liposomal doxorubicin tested in a 3D micro-engineered
tumor/blood-brain-barrier model (BBB). In Aim 2, we will leverage rodent models of invasive GBM for both
3D model validation, and testing of the efficacy of combinatorial treatment protocols in a more
physiological relevant in vivo setting. In Aim 3, we will assess our combinatorial treatment strategy to treat
spontaneous brain tumors in canine patients. If successful, this study will provide the foundation for a new
form of cancer therapy capable of surpassing conventional treatments for targeting of the bulk tumor, as
well as the infiltrative GBM cells beyond the tumor margin. If successful, this hybrid approach will eliminate
the likelihood of tumor recurrence, while preserving the vital healthy surrounding tissue and minimizing the
adverse side effects that are associated with standard therapies.

## Key facts

- **NIH application ID:** 9836618
- **Project number:** 5R01CA213423-04
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Rafael Vidal Davalos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,192
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836618

## Citation

> US National Institutes of Health, RePORTER application 9836618, High-frequency Irreversible Electroporation (H-FIRE) combinatorial GBM treatment (5R01CA213423-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9836618. Licensed CC0.

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