# Nanoparticles to reprogram innate immune cells and disrupt the metastatic niche

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $519,210

## Abstract

Summary. Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that is treated with
neo-adjuvant therapy that targets both the primary tumor and systemic disease, with subsequent
immunotherapy in the adjuvant setting. Even with the most cutting-edge therapeutic approach, approximately
20% of these patients with a pathologic complete response (pCR) will recur. Our long-term goal is to develop
strategies that target the innate immune system and aim to prevent the establishment of or destabilize sites in
which the tumor cells are protected from destruction by the immune system. Immunotherapies such as CAR-T
cells or immune checkpoint blockade have emerged as promising therapies targeting adaptive immune cells;
however, the efficacy of these treatments remains limited due to the immune protection offered at the
metastatic site by innate cells. We propose a nanoparticle (NP) strategy for targeting monocytes and
neutrophils in circulation, prior to their arrival at a metastatic niche (MN), which we propose can destabilize the
immune suppressive environment that is needed to protect tumor cells from the immune system. The scientific
premise of this application is to investigate the design of NPs to program circulating monocytes and neutrophils
that would normally travel to a MN, with programming indicating the ability to redirect immune cell trafficking
and alter immune cell polarization. Specific Aim 1 will investigate the NP design for polarization of monocytes
and neutrophils that programs an anti-tumor phenotype that leads to tumor cell clearance from metastatic
sites. Properties such as size influence the biodistribution, with the chemical composition influencing cell
interactions and polarization. We propose to initially assess internlization, the biodistribution, safety, and
persistence of NP-associated cells in the MN, the cell types that associate with NPs and the phenotypic
programming, and the impact of NPs on systemic inflammation and tumor cell numbers. We also propose to
analyze the mechanisms of NP function through assessment of i) TC recruitment and persistence in vivo, ii)
immune cell trafficking following adoptive transfer to determine the direct and indirect effects of NPs, and iii)
modulation of neutrophils numbers or phenotypes. Specific Aim 2 will investigate NP design to relieve immune
suppression at the MN and enhance/enable adaptive immune responses. We will investigate the composition
and phenotype of T cells at the MN with and without NP administration in the neoadjuvant and adjuvant setting.
Additionally, we will investigate the mechanisms by which innate cells direct T cell responses, using studies
such as depletion of T cell subsets, and performing studies to investigate T cell trafficking and persistence at
the MN. The research team includes breast cancer biologist and clinician (Jeruss), an engineer with a
successful history of translating NPs to the clinic (Shea) and am immunologist with expertise i...

## Key facts

- **NIH application ID:** 10942105
- **Project number:** 1R01EB036030-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JACQUELINE SARA JERUSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $519,210
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10942105

## Citation

> US National Institutes of Health, RePORTER application 10942105, Nanoparticles to reprogram innate immune cells and disrupt the metastatic niche (1R01EB036030-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10942105. Licensed CC0.

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