Variant signaling topology at the cancer cell–T-cell interface induced by a two-component T-cell engager

Bispecific T-cell-engaging antibodies (BiTEs) convey antigenic information from cancer to the T-lymphocyte-associated CD3 complex, thus redirecting immune effector cells to induce target cell lysis. Since antigenic information from transformed tissues is rarely unambiguous, we recently introduced novel T-cell-engaging antibody fragments called hemibodies for the combinatorial, ultraprecise targeting of cancer. 1 Here, we report the unprecedented enhancement of the plasticity of immunological synapse (IS) formation and variant signaling topology at the cancer cell–T-cell interface induced by hemibodies compared to that induced by BiTEs.