# Project 2: Clinical evaluation of a novel oHSV in recurrent human GBM

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $339,666

## Abstract

PROJECT SUMMARY – PROJECT 2
Glioblastoma (GBM) has a dismal prognosis. Based on recent favorable results with other forms of cancer,
immunotherapies are increasingly being tested in clinical trials of GBM. One type of immunotherapy consists
of oncolytic viruses (OVs0 that exert their effects by direct tumor cytotoxicity with rounds of intratumoral
infectious spread that elicit an antitumor immune response. In 2015 the first OV, based on oncolytic Herpes
Simplex Virus (oHSV), was approved by the FDA. Over the last several years, we have preclinically developed
a novel oHSV with GBM selectivity, designated as rQNestin34.5. The main difference between rQNestin34.5
and previous oHSVs that have been tested in human GBM clinical trials is that the HSV1 γ2 34.5 gene that
encodes for the ICP34.5 protein is retained under transcriptional control of a nestin promoter/enhancer element
highly expressed in GBM and in the GBM “stem-like” cell population, but not expressed in the adult human
brain. Extensive preclinical efficacy, toxicology and biodistribution studies have been carried out with
rQNestin34.5 in mice, culminating in an IND (#16380) in 2016. We are now poised to initiate a “first-in-man'
Phase I clinical trial of rQNestin34.5 for recurrent GBM, which we plan to finish by the end of this proposed
project. Our overarching hypothesis is that rQNestin34.5 in humans leads to evidence of an immune
response and that a combination of oHSV-intratumoral oncolysis/ immunostimulation with inhibition of immune
checkpoint signaling will provide increased effectiveness in animal models of glioma. We propose to test this
hypothesis with the following 3 aims: Aim 1: Test if there is a maximum tolerated dose (MTD) and pilot
correlative efficacy for a “first-in-man” clinical trial of rQNestin34.5; Aim 2: Test if immune checkpoint
(IC) blockade augments oHSV antiGBM effects in mice where T cells express high levels of PD-1; and
Aim 3: Test if expression of IC antibodies by newly engineered oHSVs improves efficacy/toxicity
profiles when compared to systemic IC antibody administration. As part of this PPG, we also plan to
collaborate with Project 4 for the correlative science required for immune cell function in human specimens
and with Project 3 for the science related to Notch signaling. Our trial will inform Project 1 in its design of the
next generation of oHSV clinical trials. We will employ the services of Core 3 for biostatistical analyses. We will
employ the services of Core 1 to generate oHSV and Core 2 for the use of glioma models. Finally, Core A
provides the overall administrative functions required to integrate and manage this project with others.

## Key facts

- **NIH application ID:** 10251083
- **Project number:** 5P01CA163205-09
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** E. Antonio Chiocca
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,666
- **Award type:** 5
- **Project period:** 2013-02-07 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251083

## Citation

> US National Institutes of Health, RePORTER application 10251083, Project 2: Clinical evaluation of a novel oHSV in recurrent human GBM (5P01CA163205-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10251083. Licensed CC0.

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