Truncated epidermal growth factor receptor (tEGFR) (tEGFR)

The truncated epidermal growth factor receptor (tEGFR) is a non-signaling, truncated version of the human EGFR protein that has been engineered to lack the intracellular tyrosine kinase signaling domain and the N-terminal ligand-binding domains I and II (Wang et al., 2011, Blood). It is primarily utilized as a versatile 'tag' in adoptive cell therapies, such as chimeric antigen receptor (CAR) T-cell therapy, to facilitate cell selection during manufacturing and in vivo tracking of the engineered cells (Paszkiewicz et al., 2016, J Clin Invest). Crucially, tEGFR serves as a safety 'suicide switch' because it retains the extracellular epitope recognized by the monoclonal antibody Cetuximab. If a patient experiences severe treatment-related toxicities, such as cytokine release syndrome, the administration of Cetuximab can selectively deplete the tEGFR-expressing CAR-T cells via antibody-dependent cellular cytotoxicity (ADCC) (Liu et al., 2019, Nature). This mechanism allows for precise control over the persistence of engineered cells without interfering with endogenous EGFR signaling in healthy tissues, as the truncated receptor cannot bind natural ligands like EGF or TGF-alpha.

Other names

EGFRtTruncated human epidermal growth factor receptorNon-signaling EGFREGFR-truncated tag

Cetuximab binds to the extracellular domain (Domain III) of the tEGFR tag expressed on engineered cells, triggering antibody-dependent cellular cytotoxicity (ADCC) to eliminate the cells.