Chlorotoxin-directed CAR T cell therapy for recurrent glioblastoma: Interim clinical experience demonstrating feasibility and safety
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.
Authors
- Julie Kilpatrick
- Jonathan Hibbard
- Brenda Aguilar (ORCID: https://orcid.org/0000-0002-6408-8422)
- Julie R. Ostberg (ORCID: https://orcid.org/0000-0001-5439-3725)
- Christine E. Brown (ORCID: https://orcid.org/0000-0003-4915-8207)
- Mishika Manchanda
- Stephen J. Forman (ORCID: https://orcid.org/0000-0002-2803-4152)
- Massimo D’Apuzzo (ORCID: https://orcid.org/0000-0001-8146-0997)
- Maryam Aftabizadeh (ORCID: https://orcid.org/0009-0001-3890-3315)
- Michael E. Barish (ORCID: https://orcid.org/0000-0003-3011-4861)
- Tracy Stiller
- Leonidas Arvanitis (ORCID: https://orcid.org/0000-0002-4744-8350)
- Jamie R. Wagner (ORCID: https://orcid.org/0000-0001-7961-3253)
- Renate Starr (ORCID: https://orcid.org/0000-0002-2200-6900)
- Behnam Badie (ORCID: https://orcid.org/0000-0001-9811-9306)
- Jinny Paul (ORCID: https://orcid.org/0000-0002-6863-6406)
- Julie A. Ressler (ORCID: https://orcid.org/0000-0003-3086-3045)
- Dongrui Wang (ORCID: https://orcid.org/0000-0002-0859-7281)
- Yichun Kong (ORCID: https://orcid.org/0000-0002-5873-6032)
- M. Suzette Blanchard
Institutions
- City Of Hope National Medical Center (US)
- City of Hope (US)
- Beckman Research Institute
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102302
- Citations
- 4
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 4.18