# TUMOR-TARGETING SALMONELLA EXPRESSING TUMOR-SELECTIVE CYTOTOXIC PROTEINS IN COMBINATION WITH PROTEASE INHIBITORS

> **NIH NIH SC3** · CALIFORNIA STATE UNIVERSITY NORTHRIDGE · 2021 · $108,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Tumor-targeting bacteria offer a number of advantages over other cancer drug delivery systems,
including targeting of multiple tumors from a distant inoculation site, selective intratumoral replication, a
high degree of attenuation and safety, and the ability to express anti-cancer proteins directly within the
tumor. Remarkably, attenuated Salmonella localize within solid tumors at levels at least 1000 times
greater than other tissues. Human clinical studies have validated the safety of intravenously
administered attenuated Salmonella mutant VNP20009, established tolerated multiple doses, and have
shown that tumor targeting occurs in some patients. However, no anti-tumor activity was observed,
even in patients in whom the Salmonella were verified to have colonized their tumors. We hypothesize
that the lack of antitumor efficacy in the human clinical trials can be overcome by engineering antitumor
apoptosis (programmed cell death) -inducing cytotoxic proteins that are able to selectively kill tumor
cells, and that the ability of these proteins to kill cancer cells can be enhanced by blocking their
degradation by tumor proteases through co-expression of protease inhibitors. The specific aims are
designed to test the tumor-selective toxin generated during the initial SC3 funding period in murine
models of cancer. The specific aims are also directed toward generation and analysis of individual
protease inhibitor combinations expressed by VNP20009 in order to prevent proteolytic degradation of
the therapeutic protein and develop tumor-targeted Salmonella vectors with enhanced antitumor
activity. VNP20009 expressing a tumor-cell targeted toxin will be analyzed alone and in combination
with one or more protease inhibitors using optical imaging of the bacterial interaction with murine tumor
models of highly aggressive breast cancer. The results are expected to indicate the effectiveness of the
targeted toxin and the effect(s) of the protease inhibitors alone and in combination with the toxin.
These results have the potential to improve VNP20009 without increasing its toxicity, and therefore
could lead to translational studies in humans.
.

## Key facts

- **NIH application ID:** 10076835
- **Project number:** 5SC3GM098207-07
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY NORTHRIDGE
- **Principal Investigator:** DAVID G BERMUDES
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $108,750
- **Award type:** 5
- **Project period:** 2013-05-10 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076835

## Citation

> US National Institutes of Health, RePORTER application 10076835, TUMOR-TARGETING SALMONELLA EXPRESSING TUMOR-SELECTIVE CYTOTOXIC PROTEINS IN COMBINATION WITH PROTEASE INHIBITORS (5SC3GM098207-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076835. Licensed CC0.

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