anti-CD123 x anti-CD3 bispecific antibody XmAb14045

An anti-CD123/anti-CD3 bispecific monoclonal antibody, in which most of the naturally-occurring Fc domain is maintained, with potential immunostimulatory and antineoplastic activities. Anti-CD123/CD3 monoclonal antibody XmAb14045 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD123, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of XmAb14045, this bispecific antibody simultaneously binds to both CD3-expressing T cells and CD123-expressing cancer cells, thereby crosslinking CD123-expressing tumor cells and cytotoxic T lymphocytes (CTLs). This may result in potent 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 on the antibody prolongs the half-life of the bispecific antibody and enhances T-cell-mediated tumor cell killing through its binding to the Fc receptors.