# Targeting tumorigenic pathways in glioblastoma with oncolytic HSV

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $395,770

## Abstract

Glioblastoma, the most malignant primary brain tumor, has remained largely refractory to all forms
of therapy, and is almost uniformly lethal with a median survival of approximately 15 months. The promise
of immunotherapy in glioblastoma has yet to be realized, in part due to altered immune activities in the
brain and the immunosuppressive microenvironment of glioblastoma. Recently isolated glioblastoma
stem cells (GSCs) are thought to be important in the tumor's ability to evade therapy. In addition, the
brain tumors they generate in mice retain many of the features of the patient tumors, so they provide a
representative tumor model for testing new therapies, something that established cell lines do not. We,
and others have developed oncolytic herpes simplex virus (oHSV) vectors that selectively replicate in
and kill cancer cells, without harming the surrounding normal tissue or causing disease, and induce anti-
tumor immune responses. The safety of oHSV has been demonstrated in clinical trials for glioblastoma;
however, while clinical responses have been very promising, approval for use in the brain has not yet
occurred, and improvements to this therapeutic strategy are warranted.
 The overall goal of our research program is to develop oHSV as therapeutic agents and elucidate
combination strategies with them that will cure glioblastoma. Building on the progress in the last funding
cycle, we propose to improve oHSV therapy by: (i) Creating new oHSV vectors that replicate efficiently
in GSCs, are safe in the brain, and are optimally immunotherapeutic; (ii) Developing new oHSV
combination strategies with inhibitors of DNA damage responses to target GSCs and take advantage of
oHSV disruption of DNA repair; and (iii) Enhancing glioblastoma immunotherapy by combining DNA
damage response inhibitors with oHSV and immune checkpoint inhibitors. Central to these studies is the
use of representative tumor models; primary and recurrent patient-derived GSCs in immunodeficient mice
and mouse syngeneic GSCs in immunocompetent mice. These studies should identify new synergistic
drug / oHSV combinations that also promote immunovirotherapy. We anticipate that therapies
demonstrated in the proposed studies will be translatable to the clinic for glioblastoma, and other brain
tumors and solid tumors in the periphery.

## Key facts

- **NIH application ID:** 9833496
- **Project number:** 5R01CA160762-07
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SAMUEL David RABKIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,770
- **Award type:** 5
- **Project period:** 2012-05-03 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833496

## Citation

> US National Institutes of Health, RePORTER application 9833496, Targeting tumorigenic pathways in glioblastoma with oncolytic HSV (5R01CA160762-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9833496. Licensed CC0.

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