# Irreversible electroporation for combinatorial GBM treatment

> **NIH NIH P01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $172,550

## Abstract

Project 3 Summary
This project will develop a combinatorial therapy that enhances high-frequency irreversible electroporation (H-
FIRE) focal ablation with targeting agents to selectively target tumor cells which infiltrate beyond the tumor
margin, a current challenge to successfully treating glioblastoma (GBM). H-FIRE is a new, minimally invasive
ablation technique that involves delivering a series of low energy (intense, but short) bursts of electric pulses 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 sharp transition between normal and necrotic tissue. Furthermore, H-FIRE only affects a single
component of the treated volume, the cell membrane, and preserves important tissue components such as
scaffolds, myelin sheaths, blood vessels, connective tissue, and nerves. We hypothesize that infiltrative cells
(beyond the H-FIRE ablated zone) can be selectively killed using a low dose of a targeted anti-GBM agent in
combination with H-FIRE, resulting in complete regression of tumors while preventing further infiltration beyond
the treatment margins. For tumor cells outside the zone of direct tissue ablation, there is a non-destructive
increase in blood-brain barrier (BBB) permeability, making these cells 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. This Project 3 of our P01 proposal has three Specific
Aims. In Aim 1, we will characterize the electrical properties of brain tumor tissues in response to H-FIRE
pulses at both the cellular and tissue scales, using a combination of engineered 3D tumor models, as well as
excised healthy (canine) and malignant (human, canine) brain tissue. We will also characterize cellular
responses to H-FIRE in combination with QUAD-CTX/Pep-1-L-CTX from Project 1 of this P01. The data
collected from this study will help accurately predict treatment volume for future H-FIRE treatments. In Aim 2,
we will quantify the effects of H-FIRE treatment in rats to assess BBB breakdown in vivo. In Aim 3, we will
assess QUAD-CTX/Pep-1-L-CTX coupled with H-FIRE 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 improving
conventional treatments for both tumors and the infiltrative GBM cells beyond the tumor margin to eliminate the
likelihood of tumor recurrence, while preserving the vital healthy surrounding tissue.

## Key facts

- **NIH application ID:** 9978745
- **Project number:** 5P01CA207206-04
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Rafael Vidal Davalos
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,550
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978745

## Citation

> US National Institutes of Health, RePORTER application 9978745, Irreversible electroporation for combinatorial GBM treatment (5P01CA207206-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978745. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*