# Selective histone deacetylase inhibition with entinostat to enhance the anti-tumor immune response to immune checkpoint inhibition in urothelial cancer

> **NIH NIH K08** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $262,296

## Abstract

Abstract:
The systemic treatment of urothelial cancer (UC) has advanced over the last several years to include the use
of immune checkpoint inhibitors for the treatment of metastatic disease. While helpful in many cases, the
majority of patients do not respond to immune checkpoint inhibitor treatment. These patients’ tumors have or
acquire the ability to suppress an active immune response despite immune checkpoint inhibition. Therefore, it
is critical to develop agents that can modulate the anti-tumor immune response toward a less suppressive
microenvironment and can combine with immune checkpoint inhibitors for more effective treatment. Entinostat
is a selective class I histone deacetylase (HDAC) inhibitor that leads to histone hyperacetylation, chromatin
remodeling, and gene expression alterations. We have preliminary data that entinostat can increase immune
gene signature expression, alter predicted neoantigen expression, and synergize with immune checkpoint
inhibition in murine models of UC. Based on these findings, a study evaluating the ability of entinostat to
promote an anti-tumor immune response in human UC tissues is warranted. Specifically, this proposal will use
a window of opportunity study of entinostat in patients with muscle-invasive UC to test the hypothesis that
entinostat can augment the antigen-driven immune response induced by immune checkpoint inhibition alone.
This hypothesis will be tested through characterization of immune gene expression, tumor neoantigens, and T
cell receptor repertoires in patients treated with entinostat plus pembrolizumab compared to patients treated
with pembrolizumab alone and compared to untreated patients. The research strategy proposed herein will
simultaneously evaluate entinostat as a promising new agent in development for UC and fulfill my short-germ
career goal of strengthening my scientific training in immunogenomic research methods. After completion of
this proposal, I will be well positioned for research independence to achieve my long-term career goal to
become a leader in genitourinary oncology with a focus on mechanism-based translational studies of novel
combinations using epigenetic and immunomodulatory agents in combination with immunotherapy.

## Key facts

- **NIH application ID:** 10132271
- **Project number:** 5K08CA248967-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Tracy L Rose
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $262,296
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132271

## Citation

> US National Institutes of Health, RePORTER application 10132271, Selective histone deacetylase inhibition with entinostat to enhance the anti-tumor immune response to immune checkpoint inhibition in urothelial cancer (5K08CA248967-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10132271. Licensed CC0.

---

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