40H3-tesirine

40H3-tesirine (40H3-TS) is an experimental antibody-drug conjugate (ADC) designed for the treatment of glioblastoma (GBM). It consists of the 40H3 monoclonal antibody, which specifically targets the epidermal growth factor receptor (EGFR), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine (SG3249). The 40H3 antibody binds to both wild-type EGFR and the EGFRvIII mutant, which are frequently overexpressed or amplified in glioblastoma. Upon binding and internalization, the tesirine payload is released, where it induces lethal DNA cross-links. Preclinical studies have demonstrated that 40H3-TS exhibits potent cytotoxicity in patient-derived xenograft (PDX) models and significant bystander killing effects in heterogeneous tumor cell populations. However, preclinical evaluations have also noted potential neurotoxicity when delivered via convection-enhanced delivery (CED).