# Large Animal Pre-clinical Models

> **NIH NIH P01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $394,263

## Abstract

Dogs and humans are the only species in which naturally occurring malignant gliomas are common. Effective
therapeutics for malignant glioma represents a major unmet need in medicine, as the prognosis for dogs and
humans with malignant gliomas remains poor. We and others have described the clinical, imaging,
histomorphologic, and molecular similarities shared between canine and human gliomas. Our collaborative
efforts have identified that canine gliomas overexpress interleukin 13 receptor alpha 2 (IL-13RA2), and
EphA2/EphA3 analogous to what has been found in human glioblastoma (GBM). Further we have been
actively investigating novel methods for loco-regional drug delivery to the brain, such as real-time MRI
monitored convection enhanced delivery, photothermotherapy, and electroporation-based approaches, and
have demonstrated the safety and feasibility of these therapeutic platforms in dogs with spontaneous gliomas.
Core 3 will provide the veterinary clinical and regulatory expertise and support to enable use of client-owned
dogs with spontaneous gliomas as a unique and unifying model system for the pre-clinical evaluation and
translation of the novel therapeutic approaches developed in Projects 1-4. We will specifically support the
projects through three specific aims. In Aim 1, we will generate IACUC protocols and obtain institutional
approvals to harvest canine tissues for use in in vitro experiments, as well as to perform the in vivo clinical
studies in client-owned dogs with gliomas described in Specific Aims 3 of both Projects 2 and 3. In Aim 2, we
will collect, clinically annotate, and bank canine glioma tissue specimens. These tissues will be distributed to
PPG project investigators to characterize the expression and distribution of IL-13RA2, EphA2, EphA3, and
EphB2 receptors in canine glioma for validation of targeting canine gliomas with the QUAD-CTX multivalent
and Pep1L-CTX cytotoxins, and optimize the electrical field thresholds required for tumor ablation using high-
frequency irreversible electroporation (H-FIRE). In Aim 3, we will provide the veterinary clinical and
neurosurgical expertise necessary to conduct pre-clinical studies to evaluate the ability of our innovative
technological platforms, the H-FIRE and convection-enhanced thermo-chemotherapy systems (CETCS), to
deliver the novel targeted cytotoxic drug conjugates, QUAD-CTX and Pep-1L-CTX generated in Project 1, to
naturally occurring intracranial gliomas in dogs, and to provide procedural training and oversight of the H-FIRE
treatment, GBM resection, and convection-enhanced delivery in the rodent models described in Projects 3
and 4.

## Key facts

- **NIH application ID:** 10220887
- **Project number:** 5P01CA207206-05
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** John Henry Rossmeisl
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $394,263
- **Award type:** 5
- **Project period:** 2017-08-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220887

## Citation

> US National Institutes of Health, RePORTER application 10220887, Large Animal Pre-clinical Models (5P01CA207206-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10220887. Licensed CC0.

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