# Tissue engineering tools for monitoring the cellular and molecular response to therapy

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $498,230

## Abstract

Summary: Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that is treated with
neoadjuvant therapy that targets both the primary tumor and systemic disease, with subsequent adjuvant
immunotherapy. Even with the most cutting-edge therapeutic approach, approximately 20% of these patients,
despite a pathologic complete response (pCR), have residual disease, present locally or in distal tissues, which
may lead to disease recurrence either locally or within distal tissues. We have devised a novel technology – a
scaffold that serves as a synthetic metastatic niche (MN) – that captures the systemic effects (i.e., immunological
changes, tumor cells) of residual disease and could be employed to monitor for disease burden, progression, or
regression. The pores of the scaffold allow for host cell infiltration and vascular ingrowth, with immune cells
attracted to the implant based on a foreign body response. In a tumor-bearing mouse, the immune cells recruited
to the implant are distinct from tumor-free mice, reflecting the changes observed in endogenous tissues (i.e.,
lung) because of systemic changes following cancer initiation and progression. These infiltrating immune cells
precede the arrival of tumor cells, prepare the site for colonization, and facilitate disease progression. We
propose that the scaffold can be used for longitudinal monitoring of disease following neoadjuvant and adjuvant
immunotherapy. Disease monitoring is based on the molecular and cellular composition within the scaffold (e.g.,
immune cells or tumor cells) that reflect the systemic impacts of residual disease. The aims of the proposal
include: Aim 1 will develop a prognostic signature that can determine response to neoadjuvant therapy and
reflect the presence of residual disease. The scaffold will supplement the histological analysis of the primary site
and can indicate the presence of residual disease through the systemic effects on cellular and molecular
phenotypes in the scaffold. The scaffold analyses will be compared with histology of patient tissue, with the goal
of identifying situations in which a pCR does not capture residual disease. In Aim 2, we propose to investigate
the use of scaffolds for surveillance of recurrence and monitoring response during adjuvant therapy. We will also
analyze the scaffold for the mechanisms that underlie the development of resistance to immune checkpoint
blockade (ICB). Identification of residual disease typically occurs when patients self-report symptoms, indicating
late-stage disease recurrence. Our platform overcomes this critical barrier by pre-defining a location to analyze
for the systemic effects of disease. Collectively, these scaffolds provide a defined site in vivo to analyze that
captures the systemic effects of residual disease on distant tissues. A solid organ, such as lung, cannot be
readily monitored over time in a patient due to the morbidity of the procedure and early metastatic foci are small
and ...

## Key facts

- **NIH application ID:** 10799694
- **Project number:** 5R01CA272940-02
- **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:** $498,230
- **Award type:** 5
- **Project period:** 2023-03-02 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799694

## Citation

> US National Institutes of Health, RePORTER application 10799694, Tissue engineering tools for monitoring the cellular and molecular response to therapy (5R01CA272940-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10799694. Licensed CC0.

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