# Utilization of Immuno-PET to detect response and guide novel oHSV-based therapy for glioma

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $542,873

## Abstract

PROJECT SUMMARY
 The overarching goal of this project is to quantify the temporal kinetics of T-cell activation and infiltration
during novel combination intratumoral oncolytic herpes simplex virus (oHSV) immunotherapy with advanced
molecular immuno- positron emission tomography (PET) imaging in preclinical models of glioblastoma (GBM).
Novel targeted oHSV immunotherapy has been shown to directly kill GBM tumor cells as the virus selectively
replicates within and lyses malignantly transformed cells, however there is a knowledge gap in understanding
the kinetics of the immune cell changes and how to harness those changes to improve therapeutic efficacy. As
inflammation and pseudo progression are key characteristics of immunotherapy-induced tumor changes,
standard imaging methods fail to provide reliable response assessments, which can sometimes take up to six
months to reveal through clinical changes in tumor size. Advanced quantitative imaging strategies can provide
spatial and temporal information on biological alterations prior to the clinically observed, downstream changes
in tumor size. Immuno- PET imaging could stratify selection of patients who pursue immunotherapy and guide
the timing and sequencing of combinatorial therapies. We have preliminary data showing that there are
differential responses in CD8 expression in gliomas during oHSV therapy and that oHSV increases CD8
infiltration, as we can image these changes with PET. Further, preliminary evidence shows that granzyme B
increases (as measured by GZP-PET) are related to overall tumor response. The overarching hypothesis is PET
molecular imaging can guide targeted IL-12 and IL-18 oHSV to enhance therapeutic efficacy and extend survival
in preclinical models of GBM. There are three specific aims to answer this hypothesis: Aim 1. Using advanced
molecular immunoPET in GBM murine models with biological validation, determine if early T-cell kinetics of
infiltration and activation are increased following oHSV therapy alone, or with oHSV expressing IL-12 and/or IL-
18. We will quantify longitudinal alterations in T-cell infiltration with [89Zr]-CD8-PET imaging of CD8+ cells and
quantify longitudinal alterations in T-cell activation (granzyme B) with [68Ga]-GZP-PET imaging. Aim 2. Using
advanced molecular immunoPET in GBM murine models, determine if secondary therapeutics (radiation therapy,
or immunomodulatory immune checkpoint inhibitors) used in combination with oHSV IOT produce increased
intermediate term T cell infiltration and activation and improve long-term tumor response. Aim 3. Determine if
secondary boosts of oHSV IOT during imaging-identified timing windows of decreased T cell infiltration and
activation can salvage therapeutic response. ImmunoPET imaging allows longitudinal quantification of
underlying immunological kinetics during oncolytic herpes simplex virus (oHSV) immunotherapy (IOT) that will
allow optimization of therapeutic regimens on a personalized basis.

## Key facts

- **NIH application ID:** 10813068
- **Project number:** 5R01CA279143-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** JAMES M MARKERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $542,873
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813068

## Citation

> US National Institutes of Health, RePORTER application 10813068, Utilization of Immuno-PET to detect response and guide novel oHSV-based therapy for glioma (5R01CA279143-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813068. Licensed CC0.

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