Fully murine knob-into-hole bispecific as surrogate molecule for drug development models

Bispecific antibodies are an exciting new class of therapeutics permitting simultaneous engagement of two distinct targets with the same antibody. A wide array of protein engineering options exist to create bispecific (or higher order multispecific) antibody constructs. The knob-into-hole (KIH) format was a pioneering format, permitting heavy-chain heterodimerization to create an “IgG with two different arms”, and derivatives of it continue to play an important role in drug development. However, researchers have lacked syngeneic mouse models for evaluating bispecific combinations as the mutations applied to human IgG1 cannot be readily transferred to murine IgG subtypes.

This poster reports the generation of a fully murine, knob-into-hole (KIH), heavy-chain heterodimerizing, bispecific antibody format. It is the first commercially available KIH bispecific antibody platform for creating fully murine surrogate molecules for syngeneic evaluation of target combinations. The poster also provides functional characterization of an anti-mCD3ε:TRP-1 bispecific antibody, capable of selectively recruiting T-cells to TRP-1+ cancer cells for increased cytotoxic effector function, as a proof of concept.

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