# Novel mouse models using MADR-GESTALT technology to accelerate glioma research

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $214,029

## Abstract

ABSTRACT (Project)
The proposed experiments leverage novel mouse models created using MADR-GESTALT technology. These
models will enhance information derived from in vivo experiments and are being applied in the following aims.
Aim 1: Evaluate rational combinations of brain penetrant receptor tyrosine kinase inhibition and immunotherapy
for study in new mouse models of oncogenically similar glioblastoma. This project will investigate mechanisms
of immune evasion following treatment with immune-based therapy, and develop rational combinations of
immunotherapeutic strategies to overcome the immunosuppressive milieu of the brain tumor micro-environment.
Immunocompetent models that accurately recapitulate the known dominant oncogenic drivers in human GBM
are crucial to this work. We propose to use the MADR-GESTALT system to create models of EGFRvIII and
CDK4/6-driven GBM in order to test how small molecule inhibitors can be effectively paired with active vaccines
and checkpoint blockade immunotherapy.
Aim 2: Establish a moderate-throughput, high-fidelity, patient-specific in vivo modeling platform using MADR in
order to understand pathogenicity of novel germline variants, their effects on gene expression, and their
contribution to pHGG susceptibility. This project seeks to determine the role of novel germline mutations in
pediatric glioma. The MADR technology will be used to develop mouse models to determine the potential of
these germline mutations to contribute to tumorigenesis. The mice will be analyzed for time to tumor
development, progression, and survival.
Aim 3: Evaluate the therapeutic potential of TCR-engineered cytotoxic T cells in H3G34R/V HGG. Previous
research has identified a small number of tumor-associated neoantigens that are presented on class I MHC and
are bound by antigen-specific T cell receptors in H3F3A mutant glioblastoma. H3F3A mutant and wild-type
models will be used to further delve into the mechanisms by which these particular mutations affect oncogenesis
in H3G34R glioblastoma, and will be used for pre-clinical testing of the efficacy of TCR-engineered adoptive T
cell transfer as targeted therapy for H3F3A mutant glioblastoma.

## Key facts

- **NIH application ID:** 10271987
- **Project number:** 3P50CA211015-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Linda M Liau
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $214,029
- **Award type:** 3
- **Project period:** 2017-08-11 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271987

## Citation

> US National Institutes of Health, RePORTER application 10271987, Novel mouse models using MADR-GESTALT technology to accelerate glioma research (3P50CA211015-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10271987. Licensed CC0.

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