DLL3 (Delta-like ligand 3) x CD3

Class

DLL3xCD3 bispecific T-cell engaging antibody (BI 764532, Boehringer Ingelheim) — parenteral formulation arm

Pathway

T-cell redirection to DLL3-expressing tumor cells (SCLC / neuroendocrine tumors)

DLL3 (Delta-like ligand 3) is a member of the Notch signaling ligand family. In normal cells it is largely sequestered inside the cell, within the Golgi apparatus, and rarely reaches the cell surface. In small cell lung cancer and related high-grade neuroendocrine tumors, DLL3 becomes abnormally displayed on the tumor cell surface, making it a distinguishing marker that is largely absent from healthy tissue. CD3 is a signaling component of the T-cell receptor complex present on essentially all mature T cells. A bispecific antibody engineered to bind both DLL3 and CD3 simultaneously acts as a physical bridge, pulling a patient's own T cells into direct contact with DLL3-positive tumor cells regardless of whether those T cells have any natural ability to recognize the tumor. This forced proximity triggers T-cell activation and release of cytotoxic proteins that kill the attached tumor cell. The rationale for this approach is that small cell lung cancer and similar neuroendocrine cancers tend to present few workable surface antigens and often evade natural immune recognition, so redirecting T cells through an artificial bridge bypasses the need for tumor-specific immune recognition. This mechanism is broadly relevant across neuroendocrine malignancies where DLL3 surface expression is a shared feature.