Seizure related 6 homolog (SEZ6) (SEZ6)

Seizure related 6 homolog (SEZ6) is a type I transmembrane protein that is predominantly expressed in the central nervous system, where it regulates neurite outgrowth, dendritic branching, and the maintenance of excitatory synapses (UniProt: P61127). While its expression in normal adult tissues is highly restricted, SEZ6 is significantly overexpressed on the cell surface of various neuroendocrine tumors, most notably small cell lung cancer (SCLC) (PubMed: 31110077). This tumor-specific expression pattern has established SEZ6 as a promising therapeutic target, particularly for antibody-drug conjugates (ADCs) designed to deliver lethal payloads to cancer cells while sparing healthy tissue. Current clinical candidates, such as ABBV-011 and ABBV-706, utilize anti-SEZ6 antibodies to internalize cytotoxic agents, leading to targeted cell death in SCLC and other high-grade neuroendocrine carcinomas (PubMed: 34155020). Although the mRNA transcript serves as a critical indicator of target density, therapeutic intervention currently focuses on the extracellular domain of the protein product.

Other names

SEZ-6BSRP-BSeizure 6-like proteinSeizure related 6 homolog mRNA

Antibody-drug conjugate (ADC) targeting the cell-surface protein to deliver a cytotoxic payload (e.g., calicheamicin or topoisomerase inhibitor) directly to tumor cells, leading to DNA damage and apoptosis (PubMed: 34155020).