Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in glioma.

ABSTRACT:

Background

Although epidermal growth factor receptor (EGFR) and its truncated, autoactive mutant EGFR variant (v)III are bona fide drivers of tumorigenesis in some gliomas, therapeutic antibodies developed to neutralize this axis have not improved patient survival in a limited number of trials. Previous studies using cells transduced to exogenously express EGFRvIII may have compromised mechanistic studies of anti-EGFR therapeutics. Therefore, we re-assessed the activity of clinical EGFR antibodies in patient-derived gliomaspheres that endogenously express EGFRvIII.

Methods

The antitumor efficacy of antibodies was assessed using in vitro proliferation assays and intracranial orthografts. Receptor activation status, antibody engagement, oncogenic signaling, and mechanism of ac

SUBMITTER: Greenall SA 

PROVIDER: S-EPMC6682217 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature