Definition

A recombinant antibody derivative composed of tri-specific T-cell activating construct (TriTAC) containing three humanized antibody derived binding domains: a N-terminal single chain Fv (scFv) that binds to the epsilon domain of CD3 antigen (CD3e) of the T-cell receptor (TCR), a middle single domain antibody (sdAb) that binds to human serum albumin (HSA) to extend the half-life, and a C-terminal sdAb that binds to human tumor-associated antigen (TAA) delta-like protein 3 (DLL3; delta like canonical Notch ligand 3), with potential immunostimulating and antineoplastic activities. Upon administration, DLL3/CD3e TriTAC HPN328 targets and binds to DLL3 on tumor cells and CD3e on cytotoxic T lymphocytes (CTLs), thereby bringing DLL3-expressing tumor cells and CTLs together, which results in the CTL-mediated cell death of DLL3-expressing tumor cells. The albumin-binding domain targets and binds to serum albumin, thereby extending the serum half-life of HPN328. DLL3, a Notch pathway protein, is overexpressed on a variety of cancer cell types while its expression is limited in normal tissues. It plays a key role in embryonic development and in tumor initiation and proliferation.