# Experimental Therapy for Brain Tumors

> **NIH NIH P01** · DUKE UNIVERSITY · 2021 · $2,542,342

## Abstract

PROJECT SUMMARY – Overall
Malignant primary brain tumors, like glioblastoma (GBM), are the most frequent cause of cancer death in
children and young adults and account for more deaths than cancer of the kidney or melanoma. Moreover,
current therapy is incapacitating and limited by non-specific toxicity. Despite hundreds of clinical trials, few
agents have been approved for clinical use, and the tumors addressed in this application remain uniformly
lethal. The OVERALL GOAL of this PPG is to develop completely new therapies or to improve existing novel
therapeutic approaches through a better understanding of the immunobiology of patient's response to both the
tumor and the therapy to achieve prolonged survival in patients with GBM without concomitant toxicity. Within
this overall goal, we have focused on eliminating the key barriers that have thus far restricted successful
immunotherapy against brain tumors. In the three proposed clinical trials, we will focus on enhancing
immunotherapy through more potent platforms, through reducing immunosuppression, through modulating the
tumor microenvironment, and through understanding the immune-mediated mechanisms activated by the
different platforms. Importantly, this PPG leverages an extraordinary group of senior scientists with a long
history of collaboration and successful translational research to accomplish these goals. Project 1, led by
John Sampson, will conduct a Phase 2 trial based on his recently published pilot trial demonstrating that
preconditioning the vaccine site with tetanus/diphtheria (Td) recall antigens prior to tumor-targeted DC
vaccination against Cytomegalovirus (CMV) antigens shown to be re-activated within the tumor dramatically
extended OS in patients with GBM. This Phase 2 trial will validate these pilot findings in a larger group of
patients. Furthermore, this trial will also incorporate a novel, fully human, clinically approved anti-CD27 mAb
that simultaneously reduces immunosuppression and potentiates vaccination through concomitant regulatory T
cell depletion and CD27 costimulation. Project 2, led by Michael Gunn, evaluates a completely novel and
extraordinarily potent cellular vaccine strategy and examines if monocyte vaccination in humans is safe and
will result in robust anti-tumor antigen-specific T cell responses. Project 3, led by Darell Bigner, will conduct a
Phase 2 clinical trial based on the promising Phase 1 work with a recombinant oncolytic poliovirus, to elucidate
mechanisms by which this therapy generates an anti-tumor immune response, and to examine the synergistic
therapeutic combination with the chemotherapeutic lomustine. These projects will be supported by an
Administrative Core, as well as three shared resource cores to provide Biostatistics and Bioinformatics
resources (Core 1), Clinical Trials and Imaging infrastructure (Core 2), and Correlative Studies and
Immune Monitoring expertise (Core 3). While the individual therapies proposed are diverse, our cent...

## Key facts

- **NIH application ID:** 10246883
- **Project number:** 5P01CA225622-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** David M. Ashley
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,542,342
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246883

## Citation

> US National Institutes of Health, RePORTER application 10246883, Experimental Therapy for Brain Tumors (5P01CA225622-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246883. Licensed CC0.

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