# Expanding CMV peptide vaccine with novel combinations and pathologies

> **NIH NIH R03** · WASHINGTON UNIVERSITY · 2024 · $77,750

## Abstract

Project Abstract
 Pediatric high-grade glioma (pHGG), diffuse midline glioma (DMG), recurrent medulloblastoma (MB),
and recurrent ependymoma are devastating diseases. The median overall survival (OS) of these diagnoses
are 8 to 12 months. Brain cancer is the most common cause of cancer death in patients aged 0-19 and
improvements in survival remain elusive. Current treatments for these malignant tumors typically entail surgical
resection or biopsy, radiation, and sometimes chemotherapy. These treatments are rarely curative. There is a
profound knowledge gap in understanding how to improve the survival and quality of life in children with these
malignant brain tumors.
 In contrast to conventional chemotherapy/radiation, immunotherapy offers a more precise treatment
approach. The human cytomegalovirus (CMV) antigen, pp65, is found in the majority of HGG and MB but not
in adjacent brain, making it a promising immunotherapeutic target. Limited data from multiple labs suggests
CMV antigens may also be present in ependymoma. However, this has not been confirmed in large samples
nor is it known if CMV antigens are preferentially expressed in certain ependymoma subtypes.
 Preliminary results from a Phase 1 clinical trial of a peptide vaccine directed at pp65 (PEP-CMV) to
treat recurrent pHGG/DMG and MB has demonstrated significant antigen-specific T cell immune responses
and prolonged clinical/imaging responses in many patients. Additionally, in an ongoing study of PEP-CMV in
adults with newly-diagnosed glioblastoma, there was a significant increase in the cytokine/chemokines G-CSF,
GM-CSF, IFN-γ, IL-10, IL-2, IL-8, MIP1-α, and TNF-α levels after PEP-CMV delivery. The addition of
checkpoint blockade has not been explored in immunotherapies targeting CMV, however, it has enhanced the
immunogenicity of cancer vaccines in preclinical brain tumor models other non-brain solid tumors.
 We hypothesize that CMV antigens are present in a subset of ependymomas and adding checkpoint
blockade to PEP-CMV will increase T cell and cytokine responses. Our objectives of this pilot study are to 1)
determine if ependymoma is a putative target of PEP-CMV and 2) improve the immunogenicity of PEP-CMV.
To attain the overall objectives, the following specific aims will be pursued. Aim 1: Establish if CMV antigens
are expressed in ependymoma. Utilizing validated and replicated methods, we will analyze 60 human
ependymoma specimens for expression of CMV antigens. Aim 2: Establish if checkpoint blockade will increase
the immunogenicity of PEP-CMV. To accomplish this, we will use a validated transgenic HLA-A2 mouse model
to determine if IFN-γ generation via ELISpot and cytokine generation responses are increased by adding
checkpoint blockade. Our long-term objective is to use data from this pilot study to conduct a Phase 1 clinical
trial of PEP-CMV plus checkpoint blockade for the treatment of recurrent ependymoma, MB, and pHGG/DMG.

## Key facts

- **NIH application ID:** 10950990
- **Project number:** 1R03NS138988-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Eric Thompson
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $77,750
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950990

## Citation

> US National Institutes of Health, RePORTER application 10950990, Expanding CMV peptide vaccine with novel combinations and pathologies (1R03NS138988-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10950990. Licensed CC0.

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