# Canine Immuno Neurotherapeutics

> **NIH NIH U01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $520,152

## Abstract

ABSTRACT:
The dog is an ideal large animal model for diagnostic and therapeutic studies and can be used to translate
successes to human patients while providing compassionate care to animals and advancing the field of
veterinary medicine. Pet dogs share their environment, and oftentimes their diet, with their owners. Dogs and
humans develop sporadic benign and malignant brain tumors at about the same rate and with similar
histopathology. Dogs are often euthanized due to the cost of care. Thus, the spontaneously occurring canine
brain tumor represents an ideal opportunity to improve the lives of people as well as pets through comparative
oncology and genomics and the “One Medicine” approach to research and direct clinical application. We propose
a multi-institutional consortium to test an innovative combinatorial immunotherapeutic approach in dogs that
spontaneously and sporadically develop malignant glial brain tumors that resemble in most important aspects,
high-grade malignant gliomas in humans. Our approach will inject a clinical grade oncolytic herpes simplex virus
(HSV) M032 that expresses human interleukin-12 (IL-12) into the resected tumor bed. Dog lymphocytes fully
respond to human IL-12 [1] and oncolytic HSV infect and kill canine (as well as mouse, non-human primate,
human) tumor cells, creating a potent local inflammatory response and an antigen-rich tumor cell debris field.
Therefore, we would anticipate that this virally-based immunotherapeutic approach would likely be as effective
in dogs with brain tumors as in humans with brain tumors. We will conduct longitudinal safety, survival and
correlative biology evaluations as a means of assessing the dog as an appropriate and informative model for
design and implementation of clinical studies in humans with high-grade malignant brain tumors. To extend these
findings, we propose, in subsequent studies, to combine the HSV immunotherapy approach with molecules that
block the action of innate checkpoint inhibitor(s). These studies are designed to address key issues of safety
and efficacy of combinatorial immunotherapy in the dog that can be translated to humans with malignant gliomas.
Malignant gliomas are the most common primary brain tumors in humans, accounting for 30% of all primary
central nervous system (CNS) tumors in adults. [2] With few major advances in decades, there has been no
significant reduction in mortality and only a modest improvement in median survival. Recently, objective
responses and long-term survivals have been observed in human glioma patients who have received oncolytic
virotherapy and a Phase I trial is currently underway at UAB in patients using M032 alone. New approaches to
utilize checkpoint inhibitors promises improved efficacy, but the ability to develop more effective combinatorial
approaches has been slow, in large part due to lack of a faithful model of spontaneous glioblastoma multiforme
(GBM) in immunocompetent hosts. Thus, the spontaneously occurring ca...

## Key facts

- **NIH application ID:** 10247895
- **Project number:** 4U01CA224151-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** M R Chambers
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $520,152
- **Award type:** 4N
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247895

## Citation

> US National Institutes of Health, RePORTER application 10247895, Canine Immuno Neurotherapeutics (4U01CA224151-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247895. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
