EGFR806-CAR T cells selectively target a tumor-restricted EGFR epitope in glioblastoma.

ABSTRACT: Targeting solid tumor antigens with chimeric antigen receptor (CAR) T cell therapy requires tumor specificity and tolerance toward variability in antigen expression levels. Given the relative paucity of unique cell surface proteins on tumor cells for CAR targeting, we have focused on identifying tumor-specific epitopes that arise as a consequence of target protein posttranslational modification. We designed a CAR using a mAb806-based binder, which recognizes tumor-specific untethered EGFR. The mAb806 epitope is also exposed in the EGFRvIII variant transcript. By varying spacer domain elements of the CAR, we structurally tuned the CAR to recognize low densities of EGFR representative of non-gene amplified expression levels in solid tumors. The appropriately tuned short-spacer 2nd generation

SUBMITTER: Ravanpay AC 

PROVIDER: S-EPMC6925027 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature