# SynerGel: A Novel Tumor Microenvironment-Modulating Hydrogel for Local Immunotherapy

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $77,282

## Abstract

PROJECT SUMMARY.
Conventional multi-modality therapy for Head and Neck Squamous Cell Carcinoma (HNSCC), such as surgery and chemoradiotherapy, can result in off-target effects and often fails to eradicate cancer, resulting in high locoregional and distant recurrence rates. The adverse tumor immune microenvironment (TIME) in HNSCC has been shown to: 1) impair tumor-infiltrating lymphocyte function, 2) decrease the production of effector cytokines, and 3) contain suppressive immunocytes. Thus, there is strong interest in developing strategies to mitigate the suppressive TIME and elicit a strong anti-tumor immune response. A successful immunotherapy approach should also boost immunological memory and thus reduce cancer recurrence. Most HNSCC patients treated with single-agent FDA-approved immunotherapies do not respond, in large part due to the immunosuppressive TIME. A drug delivery innovation that addresses immunotherapy's shortcomings while reducing side effects could significantly impact HNSCC treatment. To overcome these limitations, we propose a novel hydrogel-based platform for spatiotemporal control over the delivery of cytokines, specifically, lnterleukin-2 (IL-2), lnterleukin-12 (IL-12), and lnterleukin-15 (IL-15) to stimulate antitumor effector cells and suppress myeloid-derived suppressive cells (MDSCs). Our L-NIL functionalized multi-domain peptide hydrogel platform (SynerGel) can be injected intratumorally to deliver and release immunomodulators into the TIME locally. We hypothesize the combination of cytokines in our SynerGe/ platform will localize and extend the release of these immunomodulators intratumorally, stimulating anti-tumor effector immunocytes in synergy with the suppression of MDSCs. To investigate this hypothesis, we will evaluate SynerGe/ as an injectable, highly customizable cancer immunotherapy platform able to perform sustained delivery of multiple cytokines to the TIME (Aim 1) and identify specific immune mechanisms contributing to the efficacy of cytokine-releasing SynerGels in the HNSCC tumor microenvironment (Aim 2). We anticipate the combination of cytokines in SynerGel will have controlled release, suppress MDSCs, and stimulate anti-tumor effector immune cells for durable responses. This project offers a biomaterial-based approach to deliver immunotherapeutics to the suppressive TIME in HNSCC. Dr. Simon Young will serve as the primary mentor of the trainee with the co-mentorship of Dr. Mary Cindy Farach-Carson. During graduate degree training, the candidate will meet with mentors regularly, write first-author publications, and present research findings at conferences. This supplement will help the trainee develop scientific and communication skills, leadership qualities, and a deeper understanding of the tumor immune microenvironment in head and neck cancers, aligning with the candidate's goal of becoming an independent translational researcher.

## Key facts

- **NIH application ID:** 11064107
- **Project number:** 3R01DE030140-04S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Simon Young
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $77,282
- **Award type:** 3
- **Project period:** 2021-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11064107

## Citation

> US National Institutes of Health, RePORTER application 11064107, SynerGel: A Novel Tumor Microenvironment-Modulating Hydrogel for Local Immunotherapy (3R01DE030140-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11064107. Licensed CC0.

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