# Clinical evaluation of IL13Ra2-targeted CAR T cell therapy in combination with nivolumab in patients with recurrent malignant glioma

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $665,839

## Abstract

PROJECT SUMMARY
Chimeric antigen receptor (CAR) T cell therapy is emerging as a powerful anti-cancer strategy that may offer
new opportunities to improve outcomes for patients with malignant gliomas (MG). Although CAR T cells have
demonstrated remarkable clinical responses against hematologic malignancies, success against solid tumors
remains an important therapeutic goal. The immunosuppressive solid tumor microenvironment (TME) presents
obstacles to therapy that must be overcome in order to achieve therapeutic efficacy. City of Hope was the first
to clinically translate CAR T cells for the treatment of MG, and the lead CAR program targets the glioma-
associated antigen IL13 receptor alpha 2 (IL13Rα2). Initial findings have demonstrated that the treatment is well
tolerated and shows evidence of antitumor activity. One patient with recurrent multifocal glioblastoma (including
metastatic lesions in the spine) with characteristics of an inflamed TME, achieved a complete response (CR)
that was durable for more than 7 months. Importantly, this case provides evidence that CAR T cells can mediate
profound antitumor activity against one of the most lethal and difficult-to-treat solid tumors, and also provides
critical information on how the tumor landscape can modulate response to CAR T cell immunotherapy.
Our goal is to implement strategies to overcome the underlying causes of immunosuppression within the tumor
microenvironment that limit CAR T cell responses to MG. The PD-1/PD-L1 pathway has emerged as a critical
driver of immune suppression in solid tumors, including MG. We hypothesize that checkpoint blockade will
synergize with CAR T cells to create a tumor landscape more favorable to immunotherapy.
We propose to clinically evaluate IL13Rα2-CAR T cell therapy in combination with anti-PD1 (nivolumab) in
patients with IL13Rα2+ recurrent MG (Specific Aim 1). Interrogating correlative samples from this clinical trial,
we will assess tumor and TME changes that occur post T cell therapy with and without nivolumab, as well as
molecular pathways that dominantly correlate with response and/or resistance to therapy (Specific Aim 2). In
addition, we will preclinically evaluate in immunocompetent mice, the impact of an inflamed versus non-inflamed
TME on the efficacy of the combination therapy. These preclinical studies will aid in elucidating mechanisms of
response and resistance in the two immunological landscapes (Specific Aim 3).
This project builds upon our prior preclinical and clinical experience with IL13Rα2-CAR T cell therapy, as well as
our understanding of PD-1/PDL-1 biology and its impact on immunotherapy. We anticipate these experiments
will provide insights for improved MG therapies, which also may apply to other advanced cancers.

## Key facts

- **NIH application ID:** 9842618
- **Project number:** 5R01CA236500-02
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** CHRISTINE BROWN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $665,839
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842618

## Citation

> US National Institutes of Health, RePORTER application 9842618, Clinical evaluation of IL13Ra2-targeted CAR T cell therapy in combination with nivolumab in patients with recurrent malignant glioma (5R01CA236500-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842618. Licensed CC0.

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