Chlorotoxin-directed CAR T cell therapy for recurrent glioblastoma: Interim clinical experience demonstrating feasibility and safety

作者：Michael E. Barish, Maryam Aftabizadeh, Jonathan Hibbard, M. Suzette Blanchard, Julie R. Ostberg, Jamie R. Wagner, Mishika Manchanda, Jinny Paul, Tracy Stiller, Brenda Aguilar, Renate Starr, Leonidas Arvanitis, Julie A. Ressler, Julie Kilpatrick, Yichun Kong, Dongrui Wang, Stephen J. Forman, Massimo D’Apuzzo, Christine E. Brown, Behnam Badie · 发表于：Cell Reports Medicine · 年份：2025 · DOI：10.1016/j.xcrm.2025.102302 · 被引用次数：9 · 研究领域：CAR-T cell therapy research

A challenge in treating glioblastoma (GBM) is its phenotypic heterogeneity between patients and within tumors. Chlorotoxin (CLTX), a peptide from scorpion venom, broadly binds glioma cells through a mechanism involving surface matrix metalloproteinase-2 (MMP-2). We previously developed chimeric antigen receptor (CAR) T cells incorporating CLTX as the GBM recognition domain. Here, we report interim clinical experience of a phase 1 trial evaluating intracavity/intratumoral (ICT) delivery of CLTX-CAR T cells in four patients with MMP-2-expressing recurrent GBM (NCT04214392), with the primary objectives of feasibility and safety. The therapy is well tolerated with no dose-limiting toxicities. Three of the four participants (75%) exhibit a best response of stable disease. CLTX-CAR T cells are detected in the tumor cavity fluid and at lower levels in the blood. Human anti-CAR antibody assays do not detect humoral immunogenicity against the CLTX-CAR. These observations support further clinical evaluation of CLTX-CAR therapy.