# Reversing immune evasion and enhancing immune detection with topical resiquimod

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $438,084

## Abstract

Project Summary/Abstract
Resiquimod gel is a topically applied immunomodulator and TLR7/8 agonist. It stimulates dendritic cells (DC) in
both healthy and inflamed skin and can potently enhance immune responses. In a small phase I trial of in 12
heavily pretreated patients with refractory, skin limited cutaneous T cell lymphoma (CTCL), topical resiquimod
reversed immune evasion, improved immunodetection and induced effector anticancer responses both locally
and systemically. 90% of patients had reduction in the malignant T cell clone in treated lesions and 83% had
regression of both treated and distant, untreated skin lesions, demonstrating that this topical therapy enhances
systemic immune responses. The ability of this drug to enhance both local and systemic immune responses
suggests that topical resiquimod could be a promising new treatment for both skin infections and cancer. We
propose time sensitive, first in human ancillary studies of fresh biopsy specimens and blood samples from an
industry sponsored, multicenter, phase II, double blind, placebo-controlled trial of resiquimod gel in the
treatment of stage IA, IB and IIA CTCL. We hypothesize that topical resiquimod enhances both innate and
adaptive immune responses and we propose three Aims to study the effects of topical resiquimod on i) the
innate immune system, ii) the adaptive immune system, and iii) to discover the mechanisms by which
untreated lesions regress. We will use single cell RNA sequencing (scRNA-seq), NanoString based gene
expression profiling, multiplex immunostaining and TCR sequencing to study skin biopsies before and after
resiquimod therapy and we will use cytometry by time of flight (CyTOF), TCR sequencing and functional
assays to study blood samples before and after treatment. We will evaluate specific hypotheses that
resiquimod induces a shift in macrophage polarization from M2 to M1, activates NK cells, enhances
recruitment of T cells into skin, reverses exhaustion of T cells within the tumor microenvironment and/or
generates new tumor-specific T cells. We will determine if regression of untreated lesions is associated with
detectable levels of type I interferons or Th1 cytokines, activation of circulating DC or NK cells, or travel of
tumor-specific T cells through the bloodstream to untreated lesions. These studies are time sensitive because
they require the use of fresh biopsy specimens from an ongoing clinical trial. Our studies will clarify the
mechanisms of action of this promising new medication and determine how it reverses immune evasion and
enhances immunodetection in CTCL. These studies may support the use of resiquimod in the treatment of
other skin cancers and infections.

## Key facts

- **NIH application ID:** 10241428
- **Project number:** 5R01AR074797-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Rachael Ann Clark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $438,084
- **Award type:** 5
- **Project period:** 2018-09-07 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241428

## Citation

> US National Institutes of Health, RePORTER application 10241428, Reversing immune evasion and enhancing immune detection with topical resiquimod (5R01AR074797-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241428. Licensed CC0.

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