# Combining Irreversible Electroporation with Immunotherapy for the Systemic Treatment of Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $76,984

## Abstract

Abstract
The goal of cancer immunotherapy is to utilize the patient’s immune system to reject the invading “foreign”
tumor. However, the pancreatic cancer microenvironment is characterized by an abundance of
immunosuppressive cells and a dense stroma that prevents infiltration of anti-tumor immune cells.
Electroporation is a technique that has been utilized for decades in the laboratory; electrical voltage is applied
to cells to make holes for delivery of DNA and RNA. Irreversible electroporation (IRE) is a technique now being
used clinically for ablation of localized tumors that cannot be removed surgically (locally advanced tumors).
Our objective is to use IRE as an "in situ vaccine" to help the host recognize foreign tumor proteins
(neoantigens) and generate anti-tumor immune responses that will decrease recurrence rates. We have
utilized mouse models of pancreatic cancer to show that IRE generates anti-tumor immune cells that prevent
growth of new tumors (prophylactic immunity). We hypothesize that combining IRE with agents that augment
the immune response will result in inhibition of established, distant tumors (therapeutic immunity or “abscopal”
effects). In Aim 1, we will use mouse models to compare the effects of IRE radiation therapy (XRT), as this is
the most relevant clinical comparator. Both methods are used clinically for the ablation (killing) of locally
advanced pancreatic cancer but have been shown stimulate systemic immune responses in preclinical models.
We hypothesize that IRE will induce stronger immune responses because XRT causes fibrosis (scarring) that
will inhibit immune cell infiltration. In Aim 2, we will combine local ablation with local delivery of agents that
stimulate the innate immune system in mouse models of metastatic pancreatic cancer. In Aim 3, we will use a
novel model in which human tumors and their associated immune cells are implanted into
immunocompromised mice in order to create a “humanized” immune system. We will use this model to study
the effects of IRE on human tumors. We have assembled a multi-disciplinary team that encompasses broad
expertise in IRE, mouse tumor models, stromal biology, immunotherapy, clinical trials, and clinical careof
patients with pancreatic cancer. We envision that the combination of IRE with immunotherapy will be first
beneficial to patients with locally advanced pancreatic cancer. However, if effective, this approach may also be
beneficial to patients with metastatic disease. Since the IRE technique is already in use clinically, a clinical trial
in which one or more of the agents to be studied is delivered during or after IRE as adjuvant therapy would
likely be feasible in the near future. We will use data from the proposed research to design such a study.

## Key facts

- **NIH application ID:** 10599014
- **Project number:** 3R01CA254268-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Rebekah White
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $76,984
- **Award type:** 3
- **Project period:** 2021-01-20 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599014

## Citation

> US National Institutes of Health, RePORTER application 10599014, Combining Irreversible Electroporation with Immunotherapy for the Systemic Treatment of Pancreatic Cancer (3R01CA254268-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10599014. Licensed CC0.

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