Chlorotoxin

Venom Peptide / Tumor Targeting

Also known as: CTX, ClTx, Tumor Paint, Tozuleristide, BLZ-100

Scorpion Venom PeptidesResearch phase: Phase 2/3 (tozuleristide)Regulatory: Not approved. Tozuleristide in clinical trials for surgical glioma imaging.

Mechanism

Chlorotoxin is a scorpion venom peptide from the deathstalker scorpion that selectively binds to glioma brain tumor cells. It is being developed as a fluorescent "tumor paint" for surgical guidance.

Technical detail

Chlorotoxin is a 36-amino acid peptide from Leiurus quinquestriatus venom with four disulfide bonds. It binds MMP-2 and annexin A2 on glioma cell surfaces with high specificity. The conjugate tozuleristide (BLZ-100, chlorotoxin-ICG) is in clinical trials as a near-infrared fluorescent agent for real-time glioma visualization during surgery.

Evidence

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

    Barish ME, Aftabizadeh M, Hibbard J, Blanchard MS, Ostberg JR, Wagner JR, Manchanda M, Paul J, Stiller T, Aguilar B, Starr R, Arvanitis L, Ressler JA, Kilpatrick J, Kong Y, Wang D, Forman SJ, D'Apuzzo M, Brown CE, Badie B (2025) — Cell Reports Medicine — PMID: 40818458

    In an interim phase 1 trial (NCT04214392), intracavity/intratumoral chlorotoxin-directed CAR T cells were delivered to four patients with MMP-2-expressing recurrent glioblastoma. Therapy was well tolerated with no dose-limiting toxicities, three of four participants achieved best response of stable disease, chlorotoxin-CAR T cells were detectable in tumor cavity fluid and at lower levels in blood, and no humoral immunogenicity against the CAR was detected.

    emerging
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