# Neoantigen immunotherapy in brain tumors using anti-CD27 to deplete regulatory T cells selectively

> **NIH NIH P50** · DUKE UNIVERSITY · 2020 · $252,322

## Abstract

ABSTRACT – Project 1
In brain tumors like glioblastoma (GBM), failures to develop an effective vaccine and achieve immune
checkpoint inhibition have been attributed to both the remarkable immunosuppression and extraordinary
antigenic intratumoral heterogeneity. A major contributor to immunosuppression in GBM is elevated regulatory
T-cells (TRegs) which dramatically suppress T cell effector function and diminish the efficacy of antitumor
vaccination. Efforts to deplete TRegs by targeting the interleukin-2 receptor α (CD25) have been unsuccessful to
date, due to cytotoxic effects on effector T cells, which are required to promote antitumor immunity. To
overcome this hurdle, Project 1 builds novel preliminary data demonstrating the ability of a clinically available
CD27 agonist antibody (αCD27) to simultaneously deplete TRegs and enhance vaccine-induced immune
responses. Specifically, the Project tests the hypothesis that class I neoantigens linked to universal class II
epitopes will be well-tolerated and rendered more immunogenic by the ability of the clinically available CD27
agonist antibody to deplete TRegs and simultaneously enhance vaccine-induced immune responses in patients
with GBM. Aim 1 will evaluate the safety and therapeutic potential of a neoantigen and Cytomegalovirus
antigen vaccine in combination with dose-escalating αCD27 in patients with GBM. Cumulative results will
provide critical data on the feasibility and immunogenicity of neoantigen vaccination in patients with GBM to
determine if a larger trial is warranted. Aim 2 will determine if αCD27 simultaneously depletes TRegs and
increases vaccine-induced immune responses. It is expected that αCD27 will reduce TRegs in this patient
population while improving vaccine-induced CD8+ and CD4+ T cell responses. If successful, this work will
develop a therapeutic strategy for patients with GBM that has enhanced efficacy by addressing the issues of
host immunosuppression and intratumoral heterogeneity.

## Key facts

- **NIH application ID:** 9996535
- **Project number:** 5P50CA190991-07
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** JOHN H. SAMPSON
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,322
- **Award type:** 5
- **Project period:** 2014-09-24 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996535

## Citation

> US National Institutes of Health, RePORTER application 9996535, Neoantigen immunotherapy in brain tumors using anti-CD27 to deplete regulatory T cells selectively (5P50CA190991-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9996535. Licensed CC0.

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