Definition

An Fc-bearing, bispecific antibody-like protein directed against the tumor-associated antigen (TAA) CD123 and the human T-cell surface antigen CD3, with potential immunostimulatory and antineoplastic activities. Upon administration, anti-CD123/anti-CD3 bispecific DART molecule MGD024 simultaneously binds to both CD123-expressing cancer cells and CD3-expressing T cells, thereby crosslinking CD123-expressing tumor cells and cytotoxic T lymphocytes (CTLs). This results in the activation and proliferation of T cells and causes CTL-mediated cell lysis of CD123-expressing tumor cells. CD123, the interleukin-3 receptor alpha chain, is overexpressed in a variety of hematological malignancies; its expression is low or absent in normal hematopoietic progenitors and stem cells. The Fc domain prolongs the half-life of the agent, and a reduced affinity of CD3-binding results in less cytokine release.