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

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $428,440

## Abstract

PROJECT SUMMARY.
Immunotherapy has become an emerging standard-of-care (SOC) for many different cancer types. However,
only 15-20% of patients receive durable benefit. Other limitations include the toxicity of systemically-delivered
immunomodulators which may require frequent, high doses and lead to immune-related adverse events (irAEs).
The risk of severe, and potentially fatal, irAEs increases as the field moves towards immune/immune and
immune/SOC combination therapies. As the “front line” of tumor/immune interaction, the tumor immune
microenvironment (TIME) is a critical locus of immunomodulation, where the kinds of immunocytes in the TIME
predict the likelihood of response to diverse immunotherapies. One strategy to favorably modulate the TIME is
to localize multiple immunotherapeutics at the tumor through direct intratumoral delivery, reversing the
immunosuppressive TIME while promoting anti-tumor effector cell immunity. This can enhance local
concentration of drugs while minimizing systemic exposure and likelihood and severity of irAEs. The use of
biomaterials as platforms for cancer immunotherapy provides the potential to intelligently direct and modulate
immune cells in situ. Our drug-mimicking, peptide nanofiber hydrogel called “SynerGel” is at the forefront of this
field, with the ability to deplete suppressive immune cells while simultaneously releasing diverse factors in a
controlled manner within a specific volume. These multiple abilities allow for reduced off-target toxicity, dose-
sparing, and targeting of multiple immune pathways to address the heterogeneous nature of cancers. The overall
hypothesis of this proposal is that intratumoral injection of SynerGel renders immunologically refractory tumors
sensitive to immune-mediated killing through multiple mechanisms including: 1) optimization of local
effector/suppressor immunocyte ratios, 2) prolonged release of immune-stimulating agents, and 3) enhanced
activation of recruited effector immunocytes. We propose to improve on the efficacy of our “first generation”
MDP-based hydrogel system by designing a unique injectable, combinatorial immunotherapy platform based on
the drug-mimicking next-generation MDP hydrogel called SynerGel in three aims: Aim 1 will evaluate SynerGel
as an injectable, highly customizable cancer immunotherapy platform able to perform sustained delivery of
multiple immunotherapeutics to the TIME. Aim 2 will explore the immunologic mechanisms contributing to
SynerGel-mediated amelioration of the adverse HNSCC tumor microenvironment. Aim 3 will investigate the
combination of SynerGel immunotherapy with standard-of-care radiotherapy (RT), looking to identify specific
immune mechanisms induced by the combination of RT and immunomodulation, and allowing for effective
therapy de-escalation by eliminating the need for chemotherapy, thus decreasing toxicity. By successfully
accomplishing these aims, we hope to clarify the molecular/cellular mechanisms by which SynerGel...

## Key facts

- **NIH application ID:** 10094677
- **Project number:** 1R01DE030140-01
- **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:** 2021
- **Award amount:** $428,440
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094677

## Citation

> US National Institutes of Health, RePORTER application 10094677, SynerGel: A Novel Tumor Microenvironment-Modulating Hydrogel for Local Immunotherapy (1R01DE030140-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10094677. Licensed CC0.

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