# Combination therapy with IFN expressing oncolytic adenovirus for pancreatic cancer

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $352,275

## Abstract

Pancreatic cancer is the 3rd leading cause of cancer-related death in North America. Most pancreatic ductal
adenocarcinoma (PDAC) patients are diagnosed at an advanced stage of the disease, and treatment at these
late stages is extremely challenging. Novel therapeutics for the treatment of advanced PDAC are desperately
needed.
 In this project, we plan to develop combination therapy with interferon-expressing oncolytic adenovirus (IFN-
OAd) and chemoradiation for locally advanced and unresectable pancreatic cancer (LAPC) including borderline
resectable pancreatic cancer (BRPC), which constitute more than 50% of the PDAC patients. Treatment of local
disease in these groups will benefit the resectability and prognosis.
 We have been developing oncolytic adenoviruses (OAds) as cancer therapeutics. OAds are designed to
selectively replicate and spread within the tumor, resulting in a strong oncolytic effect mediated by the cytocidal
function of the virus leading to immunogenic cell death. OAds can also induce massive and selective expression
of a transgene in the target cancer cells where viral replication is taking place.
 Therefore, OAd system will be exploited to overcome the current obstacles of IFN-based therapy by
selectively expressing a massive amount of IFN in the tumor region. In our preliminary experiments, IFN-
expressing OAd (IFN-OAd) showed impressive tumor regression in a syngeneic PDAC model in
immunocompetent hamsters, and its effect was greatly enhanced when combined with chemoradiation. We have
also reported shrinkage induced by IFN-expressing Ad not only in the injected tumor but also in the untreated
contralateral tumor caused by the stimulation of systemic immunity. These suggest that this new combination
therapy may realize a more effective treatment of locally advanced and metastatic diseases.
 Toward this goal, we will first analyze the effects of the combination therapy in human PDAC cell lines and
the tissue-slice culture system. We then will optimize chemoradiation regimens in order to maximize the effect
of the combination therapy with IFN-OAd in an immunocompetent syngeneic hamster model. The immunological
effect and toxicity of the combination therapy will also be examined rigorously. Finally, the therapeutic benefit of
the novel combination approach of IFN-OAd with chemoradiaion will be analyzed in LAPC models as well as
with patient-derived tumor xenografts.
 This project will establish a therapeutic regimen of the novel IFN-OAd-based chemoradiation in order to
commence clinical translation in LAPC and BRPC patients. We have a strong team with a history of success in
bringing such therapeutics to patients, andonce implemented, the therapeutic/treatment will provide an excellent
opportunity to improve the current devastating clinical outcome of pancreatic cancers.

## Key facts

- **NIH application ID:** 9864051
- **Project number:** 5R01CA228760-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Julia Davydova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,275
- **Award type:** 5
- **Project period:** 2019-02-05 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864051

## Citation

> US National Institutes of Health, RePORTER application 9864051, Combination therapy with IFN expressing oncolytic adenovirus for pancreatic cancer (5R01CA228760-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864051. Licensed CC0.

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