Format chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices.

ABSTRACT: Generation of bispecific antibodies (bsAbs) requires a combination of compatible binders in formats that support desired functionalities. Here, we report that bsAb-matrices can be generated by Format Chain Exchange (FORCE), enabling screening of combinatorial binder/format spaces. Input molecules for generation of bi/multi-valent bsAbs are monospecific entities similar to knob-into-hole half-antibodies, yet with complementary CH3-interface-modulated and affinity-tagged dummy-chains. These contain mutations that lead to limited interface repulsions without compromising expression or biophysical properties of educts. Mild reduction of combinations of educts triggers spontaneous chain-exchange reactions driven by partially flawed CH3-educt interfaces resolving to perfect complementarity. This

SUBMITTER: Dengl S 

PROVIDER: S-EPMC7532213 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature