# Novel Strategies to Enhance Drug Delivery and Tumor Immunogenicity in Pancreatic Cancer

> **NIH NIH DP2** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $1,275,618

## Abstract

ABSTRACT
 Pancreatic ductal adenocarcinoma (PDAC) is a deadly form of pancreatic cancer with limited treatment
options and a low overall survival rate. Oncolytic viruses, particularly vesicular stomatitis virus (VSV), have shown
promise in treating therapy-resistant cancers, including PDAC; however, concerns about neurotoxicity and safety
have hindered its clinical application. We have developed a novel oncolytic vector platform, VMG, using virus-
directed evolution technology, which replaces VSV glycoprotein with the glycoprotein of the Morreton virus and
incorporates the M protein of the Malpais spring virus. VMG has demonstrated tumor immune modulation in
murine models and a non-neurovirulent and non-pathogenic profile in toxicology studies. The dense stroma in
PDAC, consisting of hyaluronic acid and collagen, promotes tumor aggressiveness and resistance to therapies.
Our proposed high-risk, high-reward strategy involves VMG-mediated oncolysis and the expression of
hyaluronidase and collagenase enzymes to break down the stroma, which will serve to enhance viral
biodistribution and immune cell infiltration into the tumor. This dual-stroma disruption strategy aims to improve
tumor control and patient survival. Furthermore, VMG-induced cancer cell death could enhance tumor
immunogenicity, leading to better recognition and destruction by cytotoxic T lymphocytes. We have also explored
the potential of encoding SER, a novel proteolytic enzyme, into VMG to break down the stroma and induce
immune cell infiltration. This exciting development offers new avenues for effective PDAC treatment as a
standalone approach or in combination with immune checkpoint inhibitors. Another high-risk, high-reward
strategy we plan to employ involves VMG vectors expressing murine major histocompatibility complex
alloantigens (H-2Kk, H-2Kd) in PDAC cells. This alloantigen expression is expected to trigger a potent allogeneic
immune response, leading to tumor rejection. These innovative modifications will enhance drug bioavailability,
tumor immunogenicity, and immune response against PDAC cells, potentially improving treatment efficacy in
preclinical studies and human patients. Our research addresses critical gaps in PDAC therapy and presents
novel approaches to enhance oncolytic virotherapy for this challenging cancer type. This work holds significant
potential to revolutionize cancer immunotherapy and improve patient outcomes in PDAC and other stroma-dense
and cold tumors.

## Key facts

- **NIH application ID:** 11380235
- **Project number:** 7DP2CA301099-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Bolni Marius Nagalo
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,275,618
- **Award type:** 7
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11380235

## Citation

> US National Institutes of Health, RePORTER application 11380235, Novel Strategies to Enhance Drug Delivery and Tumor Immunogenicity in Pancreatic Cancer (7DP2CA301099-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11380235. Licensed CC0.

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