The success of the BiTE format triggered the search for intellectual property space among bispecific antibody formats of similar size and valence. A potentially competing format was recently developed by the biotechnology company MacroGenics Inc and termed DART (for Dual-Affinity Re-Targeting). 8 The DART format is based on the diabody format that separates cognate variable domains of heavy and light chains of the 2 antigen binding specificities on 2 separate polypeptide chains. 9 Whereas the 2 polypeptide chains associate noncovalently in the diabody format, the DART format provides additional stabilization through a C-terminal disulfide bridge (see figure). DARTs can be produced in high quantity and quality and reveal exceptional stability in both formulation buffer and human serum. In this issue ofBlood, Moore et al conduct a side-by-side comparison of the in vitro performance of CD19xCD3 DART and BiTE molecules that were based on the same parental mouse anti–human CD3 and mouse anti–human CD19 monoclonal antibodies as blinatumomab. 1 In various redirected cytotoxicityassayswithhumanB-celllinesandautologous human B cells, the bispecific antibody in the DART format consistently outperformed the BiTE format with respect to the maximal level of B-cell lysis, the concentration required for halfmaximal B-cell lysis, and the induction of molecular markers of T-cell activation. Neither format induced the activation or proliferation of T cells in the absence of B cells. The comparison appears legitimate as the previously reported low picomolar concentrations of the BiTE format required for half-maximal target-cell lysis were confirmed. Compared with the BiTE format, the DART format revealed a moderately higher association rate constant for CD3, a moderately lower dissociation rate constant for CD19, and an ability to cross-link T cells and B cells more efficiently. The authors discuss that the more rigid configuration of the DART format with limitedflexibilitybetweenthe2antigen-binding specificitiesmayexplainthesefavorablefeatures. In addition to comparing CD19xCD3 DART and BiTE formats, Moore et al also generated and characterized a CD19xTCR DART that engages the TCR complex through an invariant epitope displayed by the TCR rather than byCD3 (seefigure). 1 Notably, theCD19xTCR DART revealed virtually identical in vitro activity as the CD19xCD3 DART and demonstrated in vivo activity based on a xenograft mouse model with human effector and target cells. While this finding along with the recently published