An NCI-designated Comprehensive Cancer Center
By City of Hope | March 17, 2020
Scorpion Venom for Brain Cancer | City of Hope Michael Barish, Ph.D., Christine Brown, Ph.D., and Dongrui Wang, Ph.D.
City of Hope researchers designed a groundbreaking CAR T cell technology that uses chlorotoxin (CLTX), a 36-amino acid peptide found in the venom of the deathstalker scorpion, to direct T cells to selectively target glioblastoma (GBM) cells. GBM is the most common type of brain tumor, and it is considered to be among the deadliest human cancers according to the American Cancer Society. A GBM diagnosis is especially alarming due to the rapid speed at which this tumor grows and disseminated throughout the brain — making it very challenging to treat.
In this study, City of Hope researchers compare CLTX binding with expression of antigens currently under investigation as CAR T cell targets, including IL13Rα2, HER2 and EGFR, on tumor cells derived from resection samples from a cohort of patients with GBM. They found widespread binding of CLTX to patient tumor cells, including the GBM stem-like cells that are responsible for tumor recurrence.
“We are not actually injecting a toxin but exploiting CLTX’s binding properties in the design of the CAR. The idea was to develop a CAR that would target T cells to a wider variety of GBM tumor cells than the other antibody-based CARs,” explained Michael Barish, Ph.D., chair and professor at Department of Developmental and Stem Cell Biology who served as the study lead.
In animal models, consistent results were found. CLTX-CAR T cells recognized and eliminated engrafted GBM tumors while bypassing nontumor cells in the brain and other organs. The highly effective and selective killing of GBM cells will bring new options to patients.
“Our chlorotoxin-incorporating CAR expands the populations of solid tumors potentially targeted by CAR T cell therapy, which is particularly needed for patients with cancers that are difficult to treat such as glioblastoma,” said Christine Brown, Ph.D., City of Hope’s Heritage Provider Network Professor in Immunotherapy and deputy director of T Cell Therapeutics Research Laboratory.
These promising findings pave the way for the first-in-human clinical trial using CLTX-CAR T cell technology. The trial primarily aims to assess the feasibility and safety of delivery of CLTX-CAR T cells in patients with recurrent or progressive GBM. The trial will also determine the optimal therapeutic dosage of CLTX- CAR T in patients. This phase I, open-label clinical trial has started enrolling patients, and it is set to be completed in 2023.
City of Hope’s commitment to research and unyielding clinical innovation played a significant role in discovering this novel CAR T cell therapy, making us one of the few to use CAR T cell therapy in brain tumors.
Have a patient who may be a candidate for a CAR T cell therapy trial?
To refer a patient, visit or call our dedicated CAR T referral line at 833-310-CART (2278).

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