# Cancer immunotherapy using injectable hydrogels for precise and tunable multidrug delivery

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $64,926

## Abstract

Project Summary
This proposal uses cutting-edge materials science and nanotechnology approaches to improve the safety and
effectiveness of cancer immunotherapy. Once cancer metastasizes, surgical removal is no longer an option and
medical interventions rarely succeed to cure or even control the disease. Fortunately, therapies that deploy the
immune system to fight cancer have led to dramatic cures in previously untreatable metastatic cancers. Patient
response to immunotherapy is highly variable, however. This is partly due to insufficient control over delivery of
immunotherapy, which is typically limited to systemic infusions that globally activate the immune system. This
poor control overstimulates the most accessible parts of the immune system, producing grave toxicity, but
inadequately stimulates less accessible anticancer immune cells. We propose to leverage an injectable hydrogel
platform we recently developed to precisely orchestrate local and controlled release of multiple immunotherapy
drugs, thereby providing an essential tool to engineer effective cancer immune responses. Immune cells evolved
to respond to highly specific spatiotemporal cues, such as cascading events, chemical gradients, and sustained
exposure to molecular “danger” signals. Since immune cells process all this information to determine whether to
continue battling or to stand down, it is essential to deliver the correct cues to the immune system in the right
way. Our approach will control both the timing and localization of cues to improve efforts to study the immune
system and deploy it therapeutically. Our preliminary studies show the feasibility of this approach: hydrogel
delivery of combination immunotherapy (TRP2 peptide, IL2 cytokine, anti-CD28 antibody, and poly(I:C) TLR3
agonist) dramatically improved survival in the poorly immunogenic B16F10 model of melanoma, whereas
standard bolus injections failed. Therefore, we hypothesize that precisely controlled and local delivery of cancer
immunotherapy will yield profound benefits in safety and efficacy.
This work uses advanced materials science approaches to develop a drug delivery platform that maximizes
therapeutic effects while minimizing immune-related toxicities. Our approach will provide a translational path
forward for combination therapies that are otherwise too toxic for clinical implementation. We will systematically
study the immune response to critical immunomodulatory agents in the context of local, sustained release. In
Aim 1, we will interrogate the impact and potential synergy of antibody combinations that specifically stimulate
the immune system’s adaptive and innate arms. In Aim 2, we will characterize the rewiring of the immune system
due to prolonged exposure to diverse toll-like receptor (TLR) agonists. In Aim 3, we will further refine our
hydrogel platform to deliver precise schedules of drug that better mimic cues seen in endogenous immune
responses. All studies will be conducted in murine models ...

## Key facts

- **NIH application ID:** 9909952
- **Project number:** 1F32CA247352-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Santiago Correa
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9909952

## Citation

> US National Institutes of Health, RePORTER application 9909952, Cancer immunotherapy using injectable hydrogels for precise and tunable multidrug delivery (1F32CA247352-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9909952. Licensed CC0.

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