# Developing macrophage reprogramming mRNA nanocarriers for initial clinical testing

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $639,059

## Abstract

Project Summary
Tumor-associated macrophages (TAMs) usually express an M2 phenotype which enables them to perform
immunosuppressive and tumor-promoting functions. Reprogramming these TAMs toward an M1 phenotype
could thwart their pro-cancer activities and unleash anti-tumor immunity, but current efforts to accomplish this
are nonspecific and elicit systemic inflammation. Our group at Fred Hutchinson Cancer Research Center has
developed a targeted nanocarrier that can deliver in vitro-transcribed mRNA encoding M1-polarizing
transcription factors to reprogram TAMs without causing systemic toxicity. With the goal of designing the first
clinical trial for treating chemotherapy-resistant ovarian cancer patients with this nanodrug, we propose here
research that will generate the data required for an IND application. Specifically, we will (1) develop a robust
protocol for the scaled-up production of genetic macrophage-programming nanoparticles under GMP-
conditions so they can be carried forward into large primate and human studies, (2) identify potential infusion
reaction risks, with reference to FDA regulations for nanomedicines, and (3) confirm safety of the nanoparticles
for clinical use in a large-animal species. We expect the outcome of the proposed research will help propel this
approach into clinical practice for the treatment of advanced ovarian cancer, and provide knowledge to design
a broad repertoire of nanotherapeutics that genetically reprogram TAMs as a strategy to treat other tumor
types.

## Key facts

- **NIH application ID:** 10884875
- **Project number:** 5R01CA263524-05
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Matthias Stephan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $639,059
- **Award type:** 5
- **Project period:** 2022-04-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884875

## Citation

> US National Institutes of Health, RePORTER application 10884875, Developing macrophage reprogramming mRNA nanocarriers for initial clinical testing (5R01CA263524-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10884875. Licensed CC0.

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