# Parametric optimization of ultrasound-mediated immuno-modulation for pancreatic cancer therapy

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $104,640

## Abstract

PROJECT SUMMARY
The immunosuppressive tumor microenvironment creates a formidable challenge to treatment of pancreatic
ductal adenocarcinoma (PDAC). Its resistance to the “gold standard” chemo- and radiation therapy and to
immune checkpoint blockade, which has recently been FDA approved for other cancer types, is motivation for
to develop new therapies for treating PDAC. Poor responses to therapy are thought to be due to paucity of
intratumoral effector T cells, which correlates with profound immunosuppression, insufficient antigen
presentation as well as desmoplasia-driven compression of tumor vasculature. Recently, non-invasive focused
ultrasound (FUS) has emerged as an immunomodulatory cancer therapy, with several studies showing primary
and metastatic tumor burden reduction after ultrasound treatment. However, lack of knowledge regarding
mechanisms of action with this very new technology as well as optimal ultrasound parameters to achieve
consistently effective immunotherapy improvement presents a barrier to clinical or even widespread preclinical
use. Furthermore, technical difficulties associated with imaging and consequently, precise treatment of
pancreatic tumors with ultrasound, have complicated preclinical studies. Here, we propose a rigorous study of
immunological biomarker changes in response to varying focused ultrasound parameters to both elucidate
optimal ultrasound parameters as well as mechanism. Therapeutic ultrasound will be varied across ablative, mild
hyperthermia, low-intensity radiation force, and cavitation regimes, with and without microbubbles. Our proposed
research will use clinically meaningful orthotopic murine models of pancreatic cancer as well as multiplex mass
cytometry-based immuno-phenotyping. Furthermore, we will use novel real-time high-resolution image-guided
therapeutic FUS technology to enable precise image guided treatment. Once we have evaluated promising
acoustic parameters, we will test the treatment protocols with immune checkpoint blockade to evaluate increase
in therapeutic efficacy. This effort will inform the optimal design of combined ultrasound-immunotherapy
strategies against PDAC.

## Key facts

- **NIH application ID:** 10375345
- **Project number:** 5R21CA246550-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Paul A Dayton
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $104,640
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375345

## Citation

> US National Institutes of Health, RePORTER application 10375345, Parametric optimization of ultrasound-mediated immuno-modulation for pancreatic cancer therapy (5R21CA246550-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375345. Licensed CC0.

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