# Engineered Ensemble Nanoimmunotherapies for Cancer

> **NIH NIH R37** · GEORGE WASHINGTON UNIVERSITY · 2023 · $451,530

## Abstract

PROJECT SUMMARY
Immune checkpoint inhibitors have revolutionized the treatment of cancer because they yield dramatic
responses and long-lasting therapeutic benefits in previously untreatable cancers (e.g. metastatic melanoma).
Despite this promise, the responses to immune checkpoint inhibitors have been restricted to small subsets of
patients and are associated with toxic, and potentially fatal immune-related adverse events. In response to this
urgent need to devise novel therapeutic strategies that dramatically increase the response rate to immune
checkpoint inhibitors, we have engineered an ensemble nanoimmunotherapy that combine the advantages of
nanotechnology and immunotherapy. Specifically, our ensemble comprises: Prussian blue nanoparticles
(PBNPs) biofunctionalized with immune adjuvants and administered in combination with systemically
administered checkpoint inhibitors. We utilize the PBNPs for photothermal therapy, which ablates tumor cells,
releasing tumor antigens, and damage-associated molecular patterns that increase tumor immunogenicity. The
loss of immunogenicity is one of the key immune escape mechanisms in cancer. Additionally, the PBNPs are
biofunctionalized to serve as a depot for local delivery of exogenous immune adjuvants, particularly toll-like
receptor agonists that play an important role in breaking tolerance to tumor antigens and improving tumor
antigen presentation, which is impaired in immunosuppressive tumors. These effects are complemented by
systemically administered checkpoint inhibitors (anti-PD-1 and anti-CTLA-4) that reverse suppression of
immune cell responses (particularly T cells) and unleash their potent antitumor effects. We believe that this
ensemble approach of targeting tumor cells, antigen presenting cells, and T cells may hold the key in
converting a non-responsive “cold” tumor to a responsive “hot” tumor. In Aim 1, we seek to determine whether
the PBNPs biofunctionalized with toll-like receptor agonists and used for photothermal therapy elicits
immunogenic cell death and improves antigen presentation. In Aim 2, we test the efficacy of the ensemble
nanoimmunotherapy on tumor eradication and preventing relapse. In Aim 3, we evaluate the efficacy of the
nanoimmunotherapy in treating disseminated cancer. The successful completion of the project will provide
critical insight into the use of multifunctional nanoparticles in combination with immunotherapies to overcome
tumor immune evasion mechanisms and improve therapeutic outcomes. Importantly, it will provide the impetus
for clinical translation of our nanoimmunotherapy, thereby extending its lasting benefits to a larger proportion of
cancer patients.

## Key facts

- **NIH application ID:** 10443229
- **Project number:** 4R37CA226171-05
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Rohan Fernandes
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $451,530
- **Award type:** 4N
- **Project period:** 2023-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443229

## Citation

> US National Institutes of Health, RePORTER application 10443229, Engineered Ensemble Nanoimmunotherapies for Cancer (4R37CA226171-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10443229. Licensed CC0.

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