# Optimization of High Frequency Irreversible Electroporation (H-FIRE) for tumor ablation and immune system activation in pancreatic cancer applications

> **NIH CA R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2026 · $513,812

## Abstract

PROJECT SUMMARY: Pancreatic cancer accounts for approximately 3% of all cancers in the United States
and approximately 7% of all cancer related deaths. New treatment paradigms are direly needed. Emerging
tumor ablation techniques have shown significant promise. This proposal will focus on High-Frequency
Irreversible Electroporation (H-FIRE), which delivers a series of electric pulses through electrodes inserted
directly into the tumor to produce structural defects in the target cell membrane resulting in cancer cell death.
The objective of this proposal is to utilize our mouse and novel pig preclinical animal models to expand upon
the preliminary data presented in this proposal and generate critical mechanistic, safety, and efficacy data
necessary to support future H-FIRE clinical trials in pancreatic cancer patients. Our overarching hypothesis
is that H-FIRE will effectively mitigate heterogeneity in physiologically and clinically relevant pancreatic
tumors, with treatments leading to contiguous zones of ablation near critical tissue structures. We further
postulate that the benefits of H-FIRE will ultimately extend beyond focal tumor ablation and generate a
predictable, tunable systemic anti-tumor immune response reducing metastatic burden and preventing
recurrence. Specific Aim 1 will characterize the biophysical response of pancreatic cancer cells and
tissues to H-FIRE. This Aim will evaluate the hypothesis that H-FIRE pulse parameters can be tuned to
achieve different cell death outcomes (apoptosis, pyroptosis, necroptosis, or necrosis) that are highly relevant
to tumor ablation, the tumor microenvironment, and anti-tumor immune responses. In concert, we will assess
ablation development with real time treatment feedback using Fourier Analysis Spectroscopy (FAST). We
expect to determine which parameters (i.e. pulse width, energized time, interphase/interpulse delay) play
significant roles in tuning cell death elicited within relevant cancer cell lines and ex viv

## Key facts

- **NIH application ID:** 11301810
- **Project number:** 5R01CA274439-04
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Irving C Allen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $513,812
- **Award type:** 5
- **Project period:** 2023-05-10T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11301810

## Citation

> US National Institutes of Health, RePORTER application 11301810, Optimization of High Frequency Irreversible Electroporation (H-FIRE) for tumor ablation and immune system activation in pancreatic cancer applications (5R01CA274439-04). Retrieved via AI Analytics 2026-07-10 from https://api.ai-analytics.org/grant/nih/11301810. Licensed CC0.

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