# Project 3: Localized microneedle-directed combination immunotherapy for cSCC

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $378,023

## Abstract

Project Summary/Abstract: Project 3
This project evaluates a novel combination immunotherapy approach applicable to a broad range of accessible
skin cancers. Specifically, we will target both a potent chemotherapeutic agent to induce immunogenic cell
death and an innate immune stimulant specifically to the 3D space of the tumor microenvironment (TME) of
cutaneous squamous cell carcinomas (cSCCs). This strategy is enabled by a dissolvable microneedle array
(MNA) device developed and produced in our laboratories. These studies represent the first tumor
immunotherapy clinical trials utilizing spatially and kinetically controlled delivery of a synergistically acting
combination therapy. This approach uniquely enables individualized patient-specific immunotherapy through
low dose localized drug delivery, obviating obstacles related to tumor and antigen heterogeneity and
reducing/preventing adverse effects associated with systemic exposure. Thus, the strategy could be applicable
to a large patient population, including those who are immunosuppressed or have or are at risk for autoimmune
diseases, as well as a broad range of skin cancers through a completely non-specific and generalizable MNA
“band-aid”-like delivery platform. Our hypothesis is that in situ MNA-directed immunotherapy (MNA-IT) will kill
tumor cells locally and induce a proinflammatory TME, enabling immune elimination of the treated tumor while
potentially inducing durable systemic immunity. It is supported by both preclinical studies and results from our
own clinical trials. To evaluate MNA-IT in patients with cSCCs, we will perform an iterative phase Ib/II clinical
trial evaluating MNA-IT single and combination therapies utilizing dissolving MNAs to deliver doxorubicin, a
STING agonist, or both directly to the TME of cSCCs. This will be evaluated in both immunocompetent
patients and in immunosuppressed transplant recipients. We will evaluate safety, clinical, and pathologic
responses, and explore therapy-induced changes in the TME and peripheral blood before, during, and after
therapy. Through forward reaching pre-clinical studies, we will develop a “next-generation” combination MNA-
IT to achieve sustained release of immune checkpoint inhibitors in the TME to support a sustained pro-
inflammatory TME favoring the induction of systemic tumor immunity.

## Key facts

- **NIH application ID:** 10469637
- **Project number:** 5P50CA254865-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Louis D Falo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $378,023
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469637

## Citation

> US National Institutes of Health, RePORTER application 10469637, Project 3: Localized microneedle-directed combination immunotherapy for cSCC (5P50CA254865-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469637. Licensed CC0.

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