QUAD 3.0-PE38QQR

QUAD 3.0-PE38QQR is a multivalent targeted cytolytic agent (immunotoxin) designed for the treatment of glioblastoma (GBM). It consists of a multivalent protein scaffold termed QUAD 3.0, which contains an IgG1 backbone, ephrinA5 (a ligand for the EphA2, EphA3, and EphB2 receptors), and a mutated version of interleukin-13 (IL-13.E13K) that binds preferentially to the IL-13RA2 receptor. This targeting moiety is site-specifically conjugated via a C-terminal cysteine to a modified form of Pseudomonas Exotoxin A (PE38QQR). By simultaneously targeting four receptors frequently overexpressed in the glioblastoma tumor microenvironment, the agent aims to address tumor heterogeneity and overcome resistance to conventional therapies. Preclinical studies in canine models of spontaneous glioma have demonstrated significant tumor shrinkage and long-term survival following administration via real-time monitored convection-enhanced delivery (CED).