# Macrophage-based ovarian cancer immunotherapy

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $358,694

## Abstract

As macrophages within the tumor microenvironment can exhibit anti-tumor or pro-tumor effects,
modulation of their behavior represents a potential therapeutic approach. This is particularly relevant in the
context of ovarian cancer progression where macrophages are a major immune cell population. While the roles
of NF-κB signaling in the regulation of tumor-associated macrophages are poorly understood, we have
reported that increased NF-κB specifically within macrophages using doxycycline-inducible transgenic mouse
models results in significant tumor cell cytotoxicity in the context of mammary or melanoma tumor cells in vivo.
We have evidence demonstrating that these effects result from both direct cytotoxic ability and effects on other
immune cells. We have begun to gain insights into the roles of NF-κB in ovarian cancer using in vivo models of
progression that recapitulate the human disease with significant peritoneal tumor implants and ascites
formation. Our findings lead us to believe that direct targeted activation of canonical NF-κB activity in
macrophages during defined stages of ovarian tumor progression will induce cytotoxic effects, improve
immune responses, and thus decrease tumor load and ascites accumulation. We will use our unique, inducible
transgenics to demonstrate the therapeutic potential of increasing macrophage NF-κB activity during ovarian
cancer progression. These findings will be used to instruct the optimization and testing of treatments
comprised of either liposomally encapsulated MTP-PE (a drug in clinical use for other indications), or of IκBα
siRNA delivered specifically to tumor-associated macrophages by nanoparticles. Both of these strategies will
increase NF-κB signaling in macrophages and limit disease progression. Our studies will test the hypothesis
that increased NF-κB signaling within macrophages in the tumor microenvironment limits tumor progression
and synergizes with clinically relevant chemotherapy and thus, represents a novel therapeutic approach.
 These studies will define the impact of increasing NF-κB signaling specifically in macrophages on the
tumor microenvironment and ovarian tumor progression and will show that targeted modulation of NF-κB in
macrophages can be harnessed as a novel therapy. These pre-clinical studies will provide critical evidence for
a novel immunomodulatory approach alone or combined with relevant chemotherapy for improving ovarian
cancer treatment.

## Key facts

- **NIH application ID:** 9879709
- **Project number:** 5R01CA214043-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** TODD D GIORGIO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,694
- **Award type:** 5
- **Project period:** 2017-03-10 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9879709

## Citation

> US National Institutes of Health, RePORTER application 9879709, Macrophage-based ovarian cancer immunotherapy (5R01CA214043-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9879709. Licensed CC0.

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