# TLR Agonist Nano-Immune Therapy for Peritoneal Metastases

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $483,556

## Abstract

Summary
Peritoneal metastases are present at diagnosis in 57% of women with ovarian cancer and 8% of patients with
colorectal cancer. Peritoneal metastases have been considered a terminal condition for the majority of patients,
but emerging evidence of immune advantages associated with intraperitoneal administration presents
opportunities to advance novel therapeutics for these cancers. Despite a strong rationale for immune therapy in
ovarian cancer, immune checkpoint inhibitors have not demonstrated efficacy in clinical trials for ovarian cancer,
and novel approaches are needed for this disease. Our preclinical studies demonstrated that intraperitoneal
delivery of mesoporous silica nanoparticles (MSN) functionalized with Toll-like receptor (TLR) agonists leads to
rapid internalization by free and spheroid-associated CD11b+ myeloid cells with subsequent trafficking to tumor
implants, rather than sequestration in the liver as seen following intravenous delivery. Furthermore,
intraperitoneal delivery of TLR agonist-modified MSN eliminated disseminated peritoneal ovarian cancer and
protected against tumor rechallenge. In contrast, subcutaneous delivery did not demonstrate therapeutic
efficacy, highlighting the impact of route of delivery and local interactions with tumor infiltrating leukocytes. This
project seeks to define mechanisms whereby intraperitoneally administered modified-MSN achieves tumor
eradication with a focus on delivery route, trafficking, toxicodynamic properties, efficacy in diverse models of
peritoneal metastases, and activation of murine and human immune cells.

## Key facts

- **NIH application ID:** 10979697
- **Project number:** 1R01CA293942-01
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Rita Elena Serda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,556
- **Award type:** 1
- **Project period:** 2024-09-09 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979697

## Citation

> US National Institutes of Health, RePORTER application 10979697, TLR Agonist Nano-Immune Therapy for Peritoneal Metastases (1R01CA293942-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10979697. Licensed CC0.

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