# Development of A Novel Imaging Strategy for Evaluation of CAR T-Cell Therapy in Glioblastoma

> **NIH NIH R21** · STANFORD UNIVERSITY · 2021 · $236,351

## Abstract

ABSTRACT
Immunotherapy has emerged as a successful therapeutic strategy for a variety of cancers. The recent success
of immunotherapies in other solid tumors has sparked increased attention to treatments targeting the immune
system in glioblastoma (GBM) and other brain cancers. One of the key challenges in the successful treatment
of brain tumors with immunotherapy is our lack of appropriate methods to visualize and quantify the killing of
cancer cells by the immune system within the brain. Currently, contrast-enhanced magnetic resonance imaging
(MRI) is used to evaluate treatment response and progression in these patients. However, the accurate
determination of tumor progression from treatment-associated inflammation, remains an unmet clinical
challenge. The lack of a useful response assessment has complicated patient care and the clinical development
of these therapies.
This proposal aims to address this by developing a novel imaging strategy to visualize and quantify the specific
protein, known as perforin, which immune cells utilize to gain access to kill cancer cells. Herein, we will develop
a first-in-class, small molecule positron emission tomography (PET) probe which is capable of passively crossing
the blood brain barrier and binding to perforin, permitting differentiation between active response to
immunotherapy and non-response. This strategy would permit non-invasive visualization of perforin levels with
minimal off-target activity as perforin is expressed exclusively by cytotoxic cells of the immune system. We will
assess the uptake and specificity of our perforin-PET probe in multiple immune cell subtypes and activation
states and in cytotoxic co-culture assays. We will then assess the utility of perforin-PET to detect therapeutic
response and predict outcomes in established, syngeneic, orthotopic mouse models of glioblastoma following
treatment with a highly promising type of immunotherapy known as chimeric antigen receptor T-cell therapy
Success of this approach would allow for rapid translation and incorporation into clinical studies. This would
permit clinicians and researchers to visualize and have real-time information of the killing of brain cancer cells
by the immune system and make informed decisions regarding the effectiveness of immunotherapy for any
particular patient. The significance of the proposed research is that it demonstrates a generalizable mechanism
to monitor multiple types of immunotherapy in glioblastoma and other brain tumors (including pediatric brain
tumors and brain metastases). Such work has the potential to improve response determination in brain tumor
immunotherapy, spare unnecessary treatment side effects, and through this eventually improve the management
of this disease.

## Key facts

- **NIH application ID:** 10189947
- **Project number:** 1R21NS121674-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Corinne Beinat
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,351
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189947

## Citation

> US National Institutes of Health, RePORTER application 10189947, Development of A Novel Imaging Strategy for Evaluation of CAR T-Cell Therapy in Glioblastoma (1R21NS121674-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189947. Licensed CC0.

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