# Project 1: Developing immune checkpoint controlled-release biomaterials for cancer immunotherapy

> **NIH NIH U54** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $101,121

## Abstract

PROJECT SUMMARY: PILOT RESEARCH PROJECT
Immunotherapies can provide effective cancer therapy, but only in a minority of patients. The clinical success of
immune checkpoint inhibitors in some malignancies has not translated to ovarian cancer. Objective response
rates for single-agent immune checkpoint inhibitor (CPI) immunotherapy clinical trials in ovarian cancer are 6-
15%. Also, treated patients experience the consequences of dysregulated immunity from systemic administration
of these agents. For cancers in which primary disease is accessible/resected, or in metastatic disease in which
lesions are accessible, controlled release immunotherapy delivered locally may provide powerful – and systemic
– anti-cancer immunity. Most anti-cancer therapies, including CPI immunotherapies, possess dose-limiting
toxicities in non-target tissues that compromise outcomes. Restricting delivery of these therapeutic agents has
demonstrated benefit with the reduction in cardiotoxicity and significant improvement in therapy through
formulation of paclitaxel into Abraxane as a clinically powerful example. We propose to develop the first
controlled release biomaterials to enable local delivery of high dose immunotherapies that would be intolerable
if systemically administered. We aim to significantly improve the frequency and durability of response following
CPI immunotherapy. We hypothesize that lower intraperitoneal immune checkpoint inhibitor concentration in
humans, relative to rodents, contributes to the low efficacy observed for ovarian cancer immunotherapies in
clinical trials. Our proposed controlled-release CPI will allow assessment in mice of the intraperitoneal dosing
concentrations relevant to humans using a novel core/shell delivery system for sustained and controlled release.
The overarching objective of this pilot project is to test improved response to cancer immunotherapy through
sustained release of immune checkpoint ligands from biomaterials that are applied locally/regionally (not
systemically). Our multi-PI complementary team aims to test this hypothesis in a rodent model of human ovarian
cancer that aligns with the exploratory and feasibility objectives of this Pilot Research Project mechanism and
appropriate to lead to a full competitive project within 3 years. Aim 1 will synthesize and characterize biomaterials
that enable the sustained release of anti-PD-L1 and can be retained locally following intraperitoneal injection to
improve immunotherapy while minimizing undesirable side effects. Aim 2 will characterize ovarian cancer
progression, immune responses, toxicity and overall survival from the sustained release of anti-PD-L1 in the
intraperitoneal cavity of rodent models that replicate aspects of human disease.

## Key facts

- **NIH application ID:** 10491934
- **Project number:** 5U54CA163072-13
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** TODD D GIORGIO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $101,121
- **Award type:** 5
- **Project period:** 2011-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491934

## Citation

> US National Institutes of Health, RePORTER application 10491934, Project 1: Developing immune checkpoint controlled-release biomaterials for cancer immunotherapy (5U54CA163072-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10491934. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*