Figure 3.

T-cell Engagers in drug discovery: (a) Optimal features in a half-life extended Next-Gen T-cell Engager. First generation TcEs such as BiTEs show very high potency, but very short half-life, and challenging manufacturability. Current half-life extended TcEs aim to show strong potency, similar to BiTEs, while also featuring manufacturability and PK properties similar to regular IgG biologics; (b) Proposed workflow for drug discovery of T-cell Engagers. Discovery of antibodies with diverse affinity and epitopes to the target is beneficial, especially of novel targets. Side-by-side function and stability profiling are recommended before and after sequence-optimization, because of the interdependent importance of both Pharmacology and CMC for the clinical success of a TcE.