Neuropilin-1 drives tumor-specific uptake of chlorotoxin.

ABSTRACT:

Background

Chlorotoxin (Cltx) isolated from scorpion venom is an established tumor targeting and antiangiogenic peptide. Radiolabeled Cltx therapeutic (¹³¹I-TM601) yielded promising results in human glioma clinical studies, and the imaging agent tozuleristide, is under investigation in CNS cancer studies. Several binding targets have previously been proposed for Cltx but none effectively explain its pleiotropic effects; its true target remains ambiguous and is the focus of this study.

Methods

A peptide-drug conjugate (ER-472) composed of Cltx linked to cryptophycin as warhead was developed as a tool to probe the molecular target and mechanism of action of Cltx, using multiple xenograft models.

Results

Neuropilin-1 (NRP1), an endocytic receptor on tumor and

SUBMITTER: McGonigle S 

PROVIDER: S-EPMC6580635 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature