# Development and validation of an autologous mouse model for the study of immune interactions with glioblastoma

> **NIH NIH R37** · UNIVERSITY OF PENNSYLVANIA · 2024 · $619,628

## Abstract

Project Summary
An adaptive immunosuppressive microenvironment is a major barrier to immune-based therapies for solid
tumors, including glioblastoma (GBM). Current model systems for preclinical development either lack substantial
components of the immune system or rely upon different species’ immune systems, which display significant
differences when compared to human immune systems. These deficiencies lead to the disconnect between
preclinical and clinical research. Here we propose to develop a humanized mouse system for the study of
immune system interactions with GBM. By taking hematopoietic stem cells from a GBM patient, we will engraft
a human immune system in mice. From the same patient, we will obtain tumor tissue and T cells. This will allow
creation of an autologous mouse system, where the components, immune system, tumor, and cell-based
therapy, all come from the same source. In doing so, we aim to avoid any complications that would arise from
cells coming from multiple individuals.
 We will validate the autologous mouse system by generating chimeric antigen receptor (CAR) T cells
from the patients’ own T cells. These redirected T cells will allow for evaluation of the model system, both in
terms of how the tumors respond to immunotherapy and how the existing immune system responds to
immunotherapy. Results in the animal model will be compared to patients receiving the same treatment, in clinical
trials at the University of Pennsylvania.
 Initial work for will focus on demonstrating the fidelity of the system to the originating tumor and immune
microenvironment, in terms of both tumor characteristics and immune system response. Thorough
characterization of immune cell subpopulations and anti-tumor activity will help identify discrepancies in the
current models as well as areas in which the new, autologous models are preferable. At the conclusion of this
project, we will have demonstrated the feasibility of using autologous materials for glioblastoma modeling and
elucidated the aspects of tumor-immune interaction that these models are most suited for use in.

## Key facts

- **NIH application ID:** 10980738
- **Project number:** 1R37CA285434-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Zev Ari Binder
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $619,628
- **Award type:** 1
- **Project period:** 2024-06-03 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980738

## Citation

> US National Institutes of Health, RePORTER application 10980738, Development and validation of an autologous mouse model for the study of immune interactions with glioblastoma (1R37CA285434-01A1). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10980738. Licensed CC0.

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