Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies.

David Kranz

David Kranz

David Kranz

+ -1 Evaluators

This paper describes a novel strategy for the rapid development of bispecific antibodies, which have seen a huge resurgence of interest over the past few years. The renewed interest has been driven by improvements in production capabilities but also in clinical results with blinatuomab, an anti-CD3/anti-CD19 single-chain antibody that not only showed efficacy but also did so at very low doses {1}. The current paper extends the technology known as "knobs in holes" developed by Carter and colleagues at Genentech. Basically, they have shown that one full-length monovalent antibody (a heavy chain with an engineered CH3 domain; i.e. knob) and a different full-length monovalent antibody (a heavy chain with an alternatively engineered CH3 domain; i.e. hole), each expressed in bacteria, will associate. Each heavy chain retained their respective light chains, thus forming a relatively homogenous, bispecific antibody. Their system worked with over 20 different bispecifics, and provided adequate quantities for pre-clinical studies. These and other new technologies for bispecific antibody production hold promise for this new generation of therapeutic agents.