# Clinical Evaluation of Chlorotoxin-redirected Chimeric Antigen Receptor (CAR) T cells for Treatment of Glioblastoma

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $768,221

## Abstract

PROJECT SUMMARY
Despite increasingly aggressive standard of care treatments, patients with glioblastoma (GBM) have a poor
prognosis that has remained unchanged for decades, and this represents a fundamental unmet medical need.
Progress in immunotherapy across a broad range of tumor types provides hope that immunological approaches,
including CAR T cell therapy, may improve outcomes for patients with GBM. This is supported by the ability of
CD19-targeted CAR T cells to eliminate B cell malignancies in the central nervous system (CNS), as well as
early clinical experiences showing safety and disease-modifying activity of CAR T cells in GBM. One major
challenge for GBM immunotherapies is the phenotypic heterogeneity of GBM tumors coupled with the scarcity
of targetable tumor-associated antigens. As an approach to address this challenge we have developed a novel
CAR that exploits the selective and broad GBM-binding properties of chlorotoxin (CLTX). CLTX is a 36-amino
acid peptide component of scorpion venom that binds specifically to GBM and other tumors with minimal cross-
reactivity to non-malignant cells. Previous early phase clinical trials have established safety of CLTX when used
as a GBM-targeting peptide for imaging and radiotherapy. Our preclinical studies demonstrate that CLTX-CAR
T cells mediate potent antitumor activity in vitro and in vivo, with no observable effector activity against normal
human cells or when adoptively transferred into cross-reactive mouse models. We now aim, in this proposal, to
clinically test the hypothesis that CLTX-CAR T cells will be safe and mediate antitumor effects when
locoregionally delivered to the CNS in patients with GBM. Aim 1 will evaluate the feasibility, safety and response
rates of CLTX-CAR T cells in patients with recurrent GBM in a phase 1 clinical trial. CLTX-CAR T cells will be
delivered locoregionally via intratumoral [ICT] and intracerebroventricular [ICV] catheters. Aim 2 will assess
CAR-mediated immunological changes associated with response and resistance. Taking advantage of our
catheter-based locoregional delivery strategy that allows sampling of the CSF throughout treatment, we will
monitor surrogate markers of CAR T cell activity, including CAR T cell persistence and changes in inflammatory
cytokines and endogenous immune subsets. We will also compare the intrinsic characteristics across different
autologous CAR T cell products with clinical response. Aim 3 will investigate pathways of GBM tumor resistance
and CAR-induced tumor evolution pre- and post-therapy, investigating antigen escape pathways and adaptive
immunosuppressive mechanisms to CAR T treatment. The innovative use of scorpion-derived CLTX for tumor
targeting would be the first example of a natural peptide−based CAR in the clinic, potentially expanding CAR
designs beyond antibody- and ligand-based targeting domains. CLTX-CAR T cell targeting of a wide range of
GBM cells within individual tumors is significant in that it will...

## Key facts

- **NIH application ID:** 10072617
- **Project number:** 1R01CA254271-01
- **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:** $768,221
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072617

## Citation

> US National Institutes of Health, RePORTER application 10072617, Clinical Evaluation of Chlorotoxin-redirected Chimeric Antigen Receptor (CAR) T cells for Treatment of Glioblastoma (1R01CA254271-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072617. Licensed CC0.

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