Delta-like ligand 3 and Cluster of differentiation 3 receptor complex (DLL3/CD3)

The Delta-like ligand 3 (DLL3) and Cluster of differentiation 3 (CD3) receptor complex is a pharmacological target assembly utilized by bispecific antibodies to treat neuroendocrine tumors. DLL3 is a Notch pathway ligand that is typically sequestered intracellularly in normal cells but becomes aberrantly expressed on the cell surface in small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (Saunders et al., 2015, PMID: 26310167). CD3 is a critical component of the T-cell receptor complex required for T-cell activation (UniProt P07766). Drugs targeting this complex, such as tarlatamab, act as molecular bridges that bring cytotoxic T-cells into close proximity with DLL3-positive cancer cells (Giffin et al., 2021, PMID: 33033110). This interaction induces the formation of an immunological synapse, leading to T-cell degranulation and the selective destruction of the tumor cell. This strategy is particularly effective in SCLC, where DLL3 expression is high and traditional therapies often fail (FDA, 2024).

Other names

DLL3-CD3Delta-like protein 3 and CD3 complexDLL3/CD3 bispecificDLL3-targeted T-cell engager

Bispecific T-cell redirection and activation leading to tumor cell lysis